While I'm still far from fully mastering StS, I've cleared A20 with Ironclad and Silent, and on around A7-10 with Defect and Watcher still working my way up on them, with Heart clears on all four characters at various ascensions. I've got over 400 hours in the game, and have been fairly active in helping provide solid and helpful advice to the community via the Steam boards, part of which is why I'm writing this guide, saves me the time of retyping everything over and over and over. If you find yourself struggling to clear the base game, or just feel like you've hit a wall somewhere in terms of climbing the ascensions, hopefully this guide will help give you some insight or a new approach to the game as a whole and help you clear that hurdle.

Before even starting the game, there are a few thing to keep in mind that might either be a help or a hindrance when looking at the overall approach to this game. If you're coming from TCG games or deckbuilders like MTG, Yugioh or Hearthstone, your first instinct is probably going to be to aim for hyper consistency, focusing on builds and kind of tunnel visioning into a certain archetype. I did the exact same thing starting out, and while it might seem like a good idea on the surface, this can really screw you over later on down the line.

Since you pick up cards as you go in StS, it's best to focus on getting a strong foundation to your deck first, making it more well rounded, and then focus on honing it towards a certain synergy or combo later on. If you focus too much on a build or archetype from the start (say going into a run saying 'I'm going to make a poison deck' right from the start) you could be missing tons of value early on because it doesn't fit the theme of 'poison'.

The main takeaway here is to build around what you already have and what the game gives you. Forget the concept of 'builds' or 'archetypes' starting out, and instead look to build synergies. This way you're not ignoring potentially good cards that might not fit a 'theme' but also are keeping an eye out for things that make already good cards even better.

While cards do a wide variety of things, they can generally be broken down into categories. There's the game's pre-defined categories, as well as what I like to call functional categories, which basically try to group cards based off of what they 'do'. For the game's pre-defined categories:

Attack: These are your basic offensive cards. They target an enemy or deal damage to multiple enemies. There are also certain cards or relics that care about this typing (Rage for example gives you 3 block for each attack played this turn).

Skills: Usually more defense or utility oriented, skill cards include cards that provide block, card draw/cycling, and other effects like poison. There are also relics and cards that care about this card type (Flechettes for example dealing damage based on the number of skills in your hand).

Power: These cards add a passive status to your character, and then remove themselves from your deck for the rest of combat. The benefit of these cards is two-fold. It gives you a permanent boost for the rest of the battle, and removing itself when played thins the deck so you can hit your important cards more consistently. As with skills and attacks, there are also relics and cards that care about the power card type as well.

Now on to the functional categories. These aren't as strictly defined as the game's pre-defined categories, more vague groupings of similar effects mostly, and there can be a bit of overlap, so one card can fill multiple roles here. Functional categories include:

Strike Plus: Not to be confused with the actual card Strike+, these cards essentially act as a strike, but with a bonus effect. Pommel Strike is a great example of this kind of card, deal damage to a single target and draw.

Block Plus: Same concept as above but with block. Shrug Off is basically just like pommel strike, but for blocking.

Front Loaded Damage: These are your cards that do big damage, but usually at a cost. Sometimes that means they just cost more energy to play, other times it's a potential downside to using the card. Cards like Carnage, Hemokenesis, Immolate, Wild Strike and Bludgeon are examples of this.

Crowd Control: These are basically cards that his multiple targets at once. This includes things like Cleave, Sword Boomerang, Immolate, Die Die Die.

Draw/Cycle: Pretty self explanatory, these are any cards that either draw or cycle cards (draw and discard effects).

Combo Pieces: These are cards that essentially can function on their own, but can also play into combos with Combo Engines. These are cards like True Grit, Hemokenesis, Offering, Reckless Strike. They all do something when you play them, but have an added effect (exhaust a card, deal damage to you, add status cards) that does something other cards care about.

Combo Engines:These cards essentially just sit there and do nothing UNLESS you have cards to work off of them with. These will usually be powers, but there are a few combo engines that aren't powers. These are cards like Rupture, Evolve, and Catalyst (gain strength when a card causes you to lose life, draw cards from drawing status cards, double/triple the enemy's current poison).

I'll go over when to take which types and when a bit later in the guide.

When you start your run, you'll be given a choice of boons to take at the start of the game. These can drastically change how a run might go, or just provide a little bit of an extra boost. Which you choose usually depends on your playstyle, how much risk you like to take, and most importantly what others you have the options of choosing from. If you did not reach the Act 1 boss, your choices will always be:

-Increase max HP
-First three encounters have 1 HP

If you had reached the boss, you could have a selection from a number of pre-set benefits, or even better rewards with a random downside attached. Since breaking down the pros and cons of each possible combo would take tons of analysis and an entire guide in itself, I'll mostly go over a few things to consider about a few key blessings.

The First 3 Encounters Have 1 HP: This is a blessing I personally take a lot, especially on higher ascensions. Since you can check your map at any time, look to see if there are any elites with less than three encounters before it. Usually this means you can essentially get a free relic (assuming a ? space doesn't throw an encounter at you instead). The main downside is you don't get a clear idea of how well your deck is functioning from an early game standpoint, and it generally has less of an impact than the other blessings if you don't use it to cheese an early elite.

Obtain a Random Rare Card: This can either be REALLY good, or just dead weight depending on the rare. It's important to note you don't CHOOSE the rare from a set of 3 like normal, the game just adds a random one to your deck. If you get something like an early game powerhouse card or something that'll be useful right away like Immolate or Wraith Form, your run is already off to a great start. If you get something like Barricade or Grand Finale? You might be better off just restarting.

Obtain a Random Common Relic: This one is usually pretty solid unless paired with a hefty downside like obtain a curse or lose all your gold. Most common relics aren't going to make or break a run. At best you get something that's just kind of useless at the start of the run but won't actively hinder you.

Obtain a Random Rare Relic: Similar to the common relic one above, but almost always has some downside attached. Getting a Dead Branch out of this can be absolutely run winning though so it's usually worth the risk in my book.

Swap Your Starting Relic With A Random Boss Relic: This one is REALLY fun to play around with. While it works better with some characters than others (Ironclad relies on the healing from his relic for sustain so he might be hurting a little more than someone like say Watcher who might not always need the extra miracles at the start of the combat). It's also great for getting the 'beat the game with one relic achievement'. Hope for a Red Key and go to town. You won't be opening chests anyway so the downside is basically moot for a one relic run.

With your blessing out of the way, it's time to go into each act.

When playing through Act 1, it's important to plan ahead. Knowing what you're potentially going to be up against is 70% of the battle here. Elites in Act 1 are almost all entirely damage races, and are as follows:

-Big Red (Goblin Nob) gets stronger when you play skills, so laying into him with attacks until it dies is usually the best way to go. Ironclad will rely on heavy damage to just burst it, Silent will use weak to mitigate damage, Defect is at a bit of a disadvantage here but can get by with smart orb uses, and Watcher just wails on it and then enters rage mode to burst down the last 50%

-Lagavullain is less pure damage it and a bit of a mix. Since it sleeps for the first 3 turns unless you smack it, you can wait a little if your opening hand is lacking. Use the first 2 turns to either set up powers or get a high damage hand, and then unload, chunking him as much as you can early. From there, try to do as much damage as you can while using one block-type card to curb his damage if needed. You want to get him as close to dead before he uses his debuff. At this stage of the game, the -1 strength/defense slows you down a LOT more than you'd think, and if you don't kill him quick, he'll do it again 3 turns later, REALLY crippling your odds of success.

-Sentinels aren't a damage race in that you need to kill them before they kill you, but more before they make your already small deck into something completely useless and full of statuses as you struggle just to draw something usable. Your first priority is nuking one Sentinel out of the fight as soon as you can (front or rear). They alternate between middle attacking on turn 1 and the outers attacking turn 2. Having strong multi-target, firebreathing, or evolve really ruins these guys.

Since most of them are damage races, focus on attack cards early until about midway through the act. From there throw in a block card or two. You're essentially looking to get at least one of each of the attack type cards:

-Strike Plus
-Crowd Control
-Frontloaded Damage

You'll also want to look to upgrade at least 2 cards. For Ironclad, Bash is almost always a great option. The extra turn of vulnerable is usually enough to cycle back to Bash and reapply this early considering your deck size. The other three really depend on what you pull.

As for bosses, here are some tips on how to prepare:

Slime Boss: Another damage race boss, you'll want to get him as close to half by turn 2, and then blast him as low as you can on his attack turn so he has less HP when he splits. Some crowd control cards are great for later in the fight, as well as front loaded damage for the pre-split phase. A firebreathing or evolve is nice for dealing with his slimed status he adds turn 1.

Hexaghost: Another damage race, you want him dead before all his flames reignite (so by turn 8ish). His opening multi-hit attack is based off of your current HP heading into the fight, so this is one of the few bosses you actually might be better off leaving yourself at 50% health and upgrading instead of resting. This is especially true if you grabbed a Disarm or similar card to lower its strength and make it's multi hit do 0 damage. Since it adds burns to your deck, firebreathing is also VERY effective against hexa.

Guardian: Guardian is the one boss you'll want to lean a little more towards defense for. It's more a battle of attrition than a damage race, though it does have a transform mechanic where once you deal X damage, it'll swap to defense mode. While in defense mode, it gains thorns so you'll take damage from attacking it, so having block to mitigate the thorns AND his attacks is important. Guardian uses a lot of multi attacks, so disarm and ways to drop his strength/weaken can be a good way to mitigate damage. Flame Barrier or Caltrops also works wonders on this guy.

At this point you'll get a choice of 1 of 3 boss relics. Most of these are usually at least useful, some more than others depending on your deck and it's strengths. A few hilights:

Velvet Choker - If you have a high cost deck and don't plan on playing more than a few cards per turn, the choker could be a nice choice if you really need that extra energy and have no other options. While there are better, its not terrible in a pinch.

Snekko Eye - With the right deck, this thing can break the game, but once you grab it you're building around it. The majority of your deck should be 2+ cost if you grab this.

Calling Bell - It's a good choice on lower ascensions where the room for error is higher, or if you have the relic that negates the next 2 curses you get, snag this thing.

Astrolable - This can be really good if you haven't removed many of your starting cards. While the cards you get from it are random, there's a good chance it'll be better than your basic strikes. A solid choice if the other options are pretty unappealing.

Philosopher's Stone - I love this relic. Giving enemies +1 str for the most part isn't a HUGE downside except for a few key enemies that really rely on multi-attacks. If your deck already has ways of weakening and mitigating damage well, you probably won't even notice much of a difference. Do note, if you do plan on going for a true final boss run, make sure you grab a good number of disarms or weakening type cards.

Coffee Drip - This is REALLY good in Ironclad since he heals 6HP after every battle with Burning Blood, and 12 with Black Blood if you get offered it as a unique boss relic. If you're really good at not taking damage, have relics that heal you in other ways like the one that heals 25% before bosses, or other way to heal like Feed/Bandage/Reaper/Self Repair, this might be a good option to take.

Fusion Hammer - Not a great option to take early, but if your deck is basically where it needs to be by the end of Act 2 it's really good, especially if you have other ways to upgrade cards like Armaments, the Anvil, etc.

Tiny House - Basically a consolation prize. Only take it if all the other options are horrible for this point in the run.

Slime Core - Pretty terrible early since you can no longer get gold. This might be better in later acts though when you have more gold or less reliant on shops.

This is where you'll start picking up some scaling damage. These are basically cards that gets stronger or make other cards more effective. Things like Inflame plus multi-hit cards, or Accuracy if you have a way to get shivs, catalyst if you can stack poison well, X cost cards if you can stockpile energy, etc. You'll also start wanting to look at what your deck does well and start looking for those combo engines. Also don't forget to look at your relics for synergies there too (Charron's ashes on exhaust, Strike Dummy on any cards with strike or build towards Perfected Strike, etc).

Act 2 is a going to test and make sure your deck can handle a variety of challenges. This is where having that well rounded deck comes into play. Birds require you to be able to hit targets multiple times, Maneating Plant punishes multi-hit decks, Shelled Parasite punishes low damage stall decks, Triple Cultist forces you to end the fight fast with strong heavy hits or good crowd control, etc. This is also where you're going to want to start focusing in on some synergies. You probably have a good balance of damage and block type cards along with some utility, and an idea of what works, as well as some relics to work with.

This is a bit harder to explain in detail since there are a TON of synergies in this game between both cards and relics, but a few cards to look out for depending on the type of deck you have:

Feel No Pain: If you have cards or relics that exhaust cards or exhaust themselves, or if you picked up a Corruption along the way, this is a great card that can do work. Since skills cost 0 with Corruption and exhausts them, you can essentially generate 3 extra block from Feel No Pain with each skill.

Demon Form: While this is usually considered a noob trap or a D-list rare by most due to the hefty 3 cost with a slow payoff, there are a few situations this is a great pick. Snekko Eye is one of them (randomizes the costs of cards from 0-3 as you draw, so its already a 3/4 chance it'll cost less). Another good time to take it is if you have a lot of ways to generate energy (Happy Sunflower, boss relics, ice cream cone, etc) and the 3 cost isn't as big of a price.

Spot Weakness: If you have a good number of multi-hit attacks, spot weakness can be an amazing card. While sometimes it does whiff (it requires an enemy to be attacking to increase your strength), its low cost and huge impact on multi-hit effects can really boost your damage potential. You're essentially adding 6 extra damage to twin strikes, 9 extra damage to boomerang blades, 12 damage to pummels, and if you have good energy generation it can make whirlwind absolutely devastating.

Body Slam: If you have a more defensive deck with lots of block options and stall, body slam is a nice card. While the unupgraded card can be a bit lackluster at 1 cost, the upgraded cost is what makes this card shine. It drops the cost to 0, meaning you can get some good free damage if you have any way of getting passive block (anchor, self forming clay, etc) or some good block cards.

While this is mostly catered to Iron Clad, the same general idea applies to all the classes. Start looking for cards that make your foundation better, and that really make what you already have pop off that much harder.

With that out of the way, its time to move on to the Elites:

Stabby Book - This is another damage race type boss, but unlike the others from act 1 that just hit hard and have a pretty static patter, this guy has a bit of a catch. His damage starts off pretty low for this stage in the game. His first hit deals about 12 damage depending on ascension level. It's more than a tickle, but definitely better than the 15-18 Lagavullain was doing in Act 1. Taking unblocked damage adds a wound to your discard pile for each unblocked hit (so a 3x4 attack would add 3 wounds if left unblocked). Annoying, sure, but still not a problem if you take him out before shuffling. The real threat is he scales. This is one of the first major enemies you can come across that has scaling damage that might not be immediately obvious (like cultists and their ritual buff for example). Eventually his numbers will get too high to effectively deal with (unless you have a VERY specific deck, and even then its a stretch), so deal with him quickly. Strength decreasing cards and weak also work wonders at cutting his scaling a little and buying some time.

Gremlin Leader - This guy can be a bit tricky since he doesn't have a set pattern. He starts the fight by summoning 2 random gremlins to fight with him. From there, his pattern depends on whether or not his minions are still alive. Depending on your deck, you can either burst him down leaving the minions to flee, or deal with the minions early which chipping him down, and get him in a loop of calling more to his aid, cutting down on the number of attacks he'll use.

Slaver Trio - These guys.... oh lord THESE guys... While they're made up mostly of enemies you've seen already, do not underestimate the slavers. They can quickly end runs for the unprepared. They all do decent mid range damage, which adds up quickly, and the middle one can add wounds to your deck. Ironically, the scariest looking one of them all is actually the least threatening. He does the least consistent damage and his only real gimmick is adding wounds. What you want to focus down is the red guy in the back. The one with the net. Usually in hallway fights he goes down fast, but with backup, you might be tempted to leave him be. Depending on your ascension level, he WILL use that net sooner or later, which will prevent you from using any attack cards the next turn. This is also usually the turn where they pump out so much damage the best way to cut it down is to take one (or more) of them out of the fight... which you now can't... because you can't attack...

The bosses in Act 2 can be massive road blocks for new players. They challenge your decks and require you to handle multiple tactics at once. Having good crowd control also becomes a much bigger priority (or some really good burst) for 2/3 bosses.

The Champ:

The Champ will test both the offensive and defensive capabilities of your deck. He hits hard, buffs himself, can gain passive armor with metallicize, and applies several debuffs to you part way through the fight, not to mention clearing all of his debuffs and boosting his attack at about half health before just going to town on you. Pacing and having consistency is key with this guy. Use the early turns to get yourself set up and use weak/block/debuffs to get yourself into a good position while chipping him down to about half. From there, unload as much as you can on him. As soon as he drops below half health, his damage output will skyrocket. Here, a good offense might be your best defense, or some really efficient block synergies.

Collector:

Collector is probably one of the more difficult of the three, but it might not seem too bad at first. They start by summoning two minions with about 40hp that attack for 10-14 damage each turn. Since they have so much health for a minion, it might be better to leave 1 alive and just deal with the extra damage rather than wasting 80 damage worth of resources, since she will summon more once they're dead. The real danger in this fight is the slow and consistent damage combined with her curse, which weakens, frails, and applied vulnerable. Having a way to gain artifact (though rare) is nice here since it make the buff slightly less effective, but you're going to want to end the fight quickly if you can. Her attacks after applying these debuffs can hit upwards of 30-40 damage in a single hit at this point, combined with the minions doing 15-20 each, it can get out of hand quickly.

Iron Golem:

This guy can be seen as either a damage race OR a battle of attrition. He starts the fight summoning 2 minions, which will either attack, guard the main boss, or use a special action to 'steal' one card from your deck (usually the most powerful). While this might initially sound bad, you can use this to your advantage since you'll know what card each one has. Upon death, the card will be returned to hand, so you can use this information to plan ahead. As for the main boss, it will attack, guard itself, and buff its own strength throughout the fight. It does start with 3 artifact as well, so keep that in mind if you're running status cards. Lastly, the main danger in this fight, is the battle is basically on a 7 turn timer. Every 7 turns, the boss will use a very powerful attack dealing about 60 damage. There's two ways to handle this. You can either try to burst down the large health bar as quickly as possible if you have good scaling, or you can focus on mitigating as much damage as you can before then in order to survive the burst, then finish the boss off in the turns following.

Act 3 is where the game really picks up in difficulty. The hallways fights become more complex, each one being almost at the level of an elite fight from prior Acts in terms of complexity. Every enemy has some sort of gimmick or tactic to deal with that's more than just attack or add guard. You have things like the black oozes that revive the following turn unless you kill all of them at once, the giant spaghetti monster who changes its intent every time it takes damage, has the scaling shield like man eating plant from act 2, and even has the ability to add the parasite curse to your deck, Transient who loses strength for each damage dealt to it, as well as small enemies that come in clusters each with their own gimmick (thorns that deal fixed damage each time they take damage, explode after 3 turns for massive damage, or add dazed cards to the deck). You also have a few returning enemies from act 2 like the sphere.

In terms of strategies, your deck is hopefully fine tuned enough to carry you through encounters without too much trouble. If the normal enemies are giving you grief, focus on fights and campfires to snag those few extra cards to fill in the gaps and upgrade the important stuff, or shops to hopefully grab relics and potions to cover your weaknesses. If your deck is in good shape, there can be some REALLY good events in Act 3, though also some pretty devastating ones so it's a bit of a mixed bag on what to go for, but the odds are in your favor for getting some extra relics just from events.

Lastly, take note of the boss you'll be facing, since the Act 3 bosses are the most varied of the bunch in terms of strategies and how to approach them, but I'll get more into that in the next section.

Elites:

The elites in Act 3, much like the enemies, are much more complex in terms of strategies, and all of them can be run ending for the unprepared. If you're not confident in your deck, I'd advise avoiding Act 3 elites entirely if at all possible.

Stone Head:

Stone head is a bit of a damage race, but with an absolutely massive health bar. The trick to this fight is noticing it's affected by slow. This means that every time you play a card, the next card that turn will do a slightly higher amount of damage. Play order is extremely important, and you'll want to play your most damaging cards last to take full advantage of this. The first 5 turns it will count down, doing relatively low damage attacks, debuffing you, as well as some other actions. Once that countdown is over though, be ready because it will relentlessly attack with high damage blows until only one of you is left standing.

Nightmare:

This is probably one of the easier Act 3 Elites. The main gimmick is every other turn it gives itself intangible, meaning all damage effects only do 1 damage that turn. Use those turns to prepare for the following turn and focus on blocking the high damage it puts out. Hand and deck manipulation are great against this elite since you can rig a high damage turn for when it's vulnerable.

Reptomancer:

It's almost meme-worthy how much trouble she gives people. Almost everyone I've discussed this elite with actively avoided Act 3 elites early on just to avoid dealing with it. At the start of the fight she will have 2 daggers summoned. The daggers have a very simple pattern. Turn 1, low damage, turn 2, kamikaze into you for 25+. Reptomancer herself alternates between summoning daggers (one on each of the first two turns usually), and high damage attacks. Your goal is to nuke the daggers ASAP while still putting out some damage to repto. Multi-target attacks are amazing for this fight, and Immolate makes really short work of the daggers.

These are some of the toughest fights in the game, and require a bit of planning and forethought going into it. Knowing what you're up against at the start can definitely help you better prepare and fill some holes in the deck if need be. If there's a shop close to the boss, I highly recommend grabbing a few potions to give you that extra edge if you have any open slots (fairy in a bottle, entropic brew, strength or dex potions, or if you have certain key cards you need to synergize for scaling like Demon Form, liquid memories).

Awakened One:

This is arguably the hardest of the three, though ironically the one I tend to have the least issues with. The fight starts off with two cultists and the boss. You'll want to deal with the cultists first, since they will continue to scale throughout the fight, and then deal with the boss itself. Important to note is the boss's passive ability. Using powers will permanently increase it's strength by 2, so unless it's a power that is ABSOLUTELY necessary for your deck to function, hold off temporarily. Don't worry, you'll have your chance to power up and unload. From there, use a combination of weak and cost effective block to mitigate damage while wearing it down, or scaling up hard with cards like spot weakness (this boss is the exact reason I don't rely ONLY on Inflame for strength buffs on Ironclad). Kill it, and then wait. The next turn it will revive in it's awakened form. This is where the real fight begins.

The passive is gone, so feel free to use the rest of your powers while trying to take it out as quickly as possible. Its first turn it will add a void to your deck, which when drawn reduces your energy for the turn by 1. If you have a thicker deck, or even just a midsized deck, this isn't likely to be a huge issue but I do tend to have pretty bad luck and draw it relatively close to when it's added. Once you chunk its health down again the fight is finally over.

Deca Donu:

These two bring scaling to a whole new level. Going into the fight knowing what to prioritize is 70% of the battle. Each turn they alternate between attacking and supporting each other. So one turn, Deca will attack and Donu will increase both their strength by 3. The following turn, Donu will strike and Deca will apply block to both, repeat until death. Donu is your primary target from the start. Without the scaling, the damage from Deca should be pretty easy to deal with, assuming you take him out before the buffs get out of hand. Malaise is actually an amazing card for this fight, since after killing one, you can malaise the other and remove a good portion of the buffs permanently. Also, corpse explosion is incredible here since you'll only have to kill ONE of them (though on higher ascension they start with artifact, so keep that in mind).

Time Eater (AKA Gary says 'stop having fun')

Time Eater was the hardest boss for me to figure out how to fight, but once you understand how he works, it's definitely the easiest of the three. There is a counter under his health bar by his status effect with a clock. This will count up from 0 to 12 every time you play a card. At 12, he ends your turn and gains 2 strength. This can be a problem for infinite decks or decks that just like to play a ton of cards, or if you've build some sort of Gube Goldberg machine in deck form. Smart play and careful planning is the name of the game here. Make the most of each turn, limiting yourself to 5-6 cards per turn. If need be, use one turn where you don't have many damage cards or optimal plays to set up for the following turn. Also, never end a turn with the counter on 10 or 11. Even if you don't NEED to play a card, if you're sitting at 11, just play it so you can make the most of your next turn.

He also has some nasty tricks up his sleeve in terms of status effects. He can reduce your card draw by 1, and this effect will likely be there for the entire fight considering how often he reapplies it, so some form of deck manipulation or exhaust cards to help thin out your deck are great to help consistency. Once he's below half, stop attacking. On his next turn he will heal back to 50%, so make him waste that healing by getting maybe 1-15hp out of it, instead of 100-200 if you really chunk him (unless you can take him from half to dead in one turn, then just end the fight there). He also has a few multi-hit attacks so cards like flame barrier and caltrops are great too.

Once you clear the game with the three main characters (everyone but watcher), three keys will be added to the spire. One is obtained by killing a super elite (the burning elite icon on the map) which gives the elite an added bonus (20% more health, health regen, metalicize, more strength, etc), one you get by using a campfire action, and the last one you get by taking it instead of a relic from a chest location on the map. Will all three keys in hand, the way to Act 4 will open upon killing the Act 3 boss. Act 4 is incredibly short, but is difficult and will push your deck building skills to the limit. While difficult, beating this challenge will unlock the beta art for that character's deck, which is an amazing reward (Double Tap for example being two running sink faucets, ie water from the 'tap'). One does not simply 'clear' Act 4 though, this is something you spend the entire run preparing and working towards. There are only 2 fights to deal with, a campfire at the start, and a shop. The elite and boss are essentially back to back though, so be prepared for a grueling experience.

Elite:

This is an interesting fight since for the only time in the game, you're caught between two enemies. You have the shield bearing enemy on your left and the spear on your right. Both can dish out heavy damage, and have ways to buff one another. The gimmick is the one you're facing away from will deal more damage, and you can turn towards them by using single target cards on that enemy. Keep this in mind as you attack to mitigate their damage. I personally go for the shield first, since it has some really nasty debuffs, a huge damage single hit attack, and can block both of them for a good chunk. Corpse explosion once again shines here, but multi attacks and multi target work wonders, as does poison since it gets around guard.

Boss:

The true final boss is intimidating, even if you know what you're doing, let alone going in blind. It has more health than anything you've fought up to this point, and two really nasty passives. Lets break it down piece by piece.
Beat of Death: The number next to it indicates how much damage the passive will do, and starts higher as you climb higher ascensions. It will deal that much damage every time you play a card. Now it's important to note the card effect ALWAYS happens first, so if you play a block card, you'll gain the 5 block, THEN take the 1 damage. Use this to your advantage to take as little damage as possible from playing cards. This damage is also mitigated by any kind of damage reduction from relics (Tungsten Rod for instance will reduce this damage by 1).
Damage Cap: There's a 300 damage cap the boss can take each turn. This is definitely going to throw a wrench into your plans if you go infinite and rely on that (as will the constant chip damage from Beat of Death), so be prepared to see its entire move set at least once even if you can pump out massive damage numbers.

With the passives out of the way, on to the flow of the fight. The boss has a standard pattern it cycles through. It will always start by applying 2 vulnerable, weak and frail, and then add one of each status card to your deck. While annoying, it more sets up for the boss's next two turns. From there, it will use a multi hit attack. This attack only does 2 damage.... 12 times... and this is where the preparedness comes in. It's very easy with the right setup to get the boss to practically kill itself with this attack. Thorns stacking through caltrops, relics, flame barrier, etc can essentially chunk the boss's health while you just block. Combine this with the Torri/Tungsten combo to nullify the damage entirely and you've just trivialized the boss, well... the first attack cycle anyway. After this, it'll do a single hit large chunk damage attack for 40. Without ways to deal with statuses, keep in mind you're still vulnerable for this so you'll be taking 3x12 and 60 damage from these instead. From there, it removes all strength debuffs/losses (this includes things like disarm and malaise), buffs its strength by 2. It also adds another buff depending on how many cycles it has gone through. The first cycle it adds artifact, then increases beat of death, then adds painful stabs (stabby book's passive of adding wounds for each unblocked damage), then just massive increases in strength if you're somehow still alive.

Your goal is to end the fight ASAP while using his multi-hit against him, or optimizing as much damage for the least amount of energy so you can save some for blocking. To do this, you'll want a deck that can get rolling quickly with little setup (so unless its innate and in a snekko eye deck, maybe skip that Demon Form), and good block cards. Your standard blocks aren't going to cut it here.