Hard Requirements:

[1] Unlocking Every Character
[2] Beat the Normal Ending as all Characters
[3] Beat the True Ending for most Characters
[4] Unlock the Dream Route (True Ending needs to be done first for that character)
[4] Completing every Curse based Challenge (listed below)
[5] Unlock X Must Die Difficulty
[6] Sudo Requirement (Highly Recommened): Unlock Axel's, Fuji's, or Boss's Curses

Necessary Challenges

Any requirements to unlock these will be listed in the challenge book

• Assignment Anya
  
• Massive Attack
  
• Gauntlet
  
• Jumbled Mess
  
• Blackout
  
• Old Grounds
  
• Hemophilaic
  
• Mutants
  
• No Spill Blood
  
• Mom's Credit Card
  
• Great Depression
  
• Arcade Maniac

You only have really three options: Axel, Fuji or Boss. Everyone else while doable is just not worth the effort.

It is also recommend to have all personal curses on for either Boss or Fuji because with all general curses activated some of the personal ones downsides are either completely negated or will already have happen anyways.

Benefits of Axel:

• Can easily deal with Chunks due to his ice hatchets stun effect.
  
• Ice hatchets can also stun enemies which helps with stronger enemies .
  
• The hideaway can give a free item and gives guaranteed free health and ammo.

Benefits of Boss:

• Explosions become really powerful late game (may cause lag)
  
• Curse of the Mysterious is a freebie since the whole map will be hidden (Caused by X Must Die)
  
• Boss Mid-Late Game can screen wipe any room and one shot any boss
  (Besides the final boss, Golden Mask, and The Glitch).

Benefits of Fuji

• Curse of the Hunted negates Long Distance Relationships downside/Cordelia's shop spawning only some times. This means free items every floor (besides alt) and sometimes two shops.
  
• Money is only necessary for Doctor upgrades
  
• Curse of Heavy Weight is almost canceled out by Curse of the Hoard
  
• The shop gives a free map which will make navigation super easy.
  
• Free Health at Shop.
  
• Free Items at shop.

Who Should you Choose?
Fuji is without a doubt better than Boss and Axel simply due to the Free Shop Curse and a guaranteed shop spawn on all floors (except ALT).

This is a big deal because the only thing you need to buy is doctor health and strength upgrades meaning anything money related is pointless beyond that. This makes any money based curse negligible really quickly.

Map also being free allows navigation to become possible since without it your blind.

Ambrosia also being free means any Portrait Demon hits or close calls can be negated at least once.

Chunks also spawns almost a minute after you spawn which Fuji is more adept at taking out early game. Axel is also good against Chunks due to his ice hatchets stunning him but that benefit is lost on the dream floors due to no more Chunks.

Fuji is only worse when dealing with the final boss due to the range of her fists and of that because Boss is way better for killing the final boss due to the range of explosives.

TL;DR Overall Fuji is better due to her benefits remaining consistent, free items, and in a way less luck dependent. Boss is next best choice for damage and a smooth run late game. Axel is great if you struggle early game.

General Challenges you will Encounter at all floors

• Facing Chunks (Will not be encounter in Dream Floors)
  
• Facing Portrait Demon (Will not be encounter in Dream Floors)
  
• No idea where you are
  
• Anything you will encounter in a normal run but worse

General Tips

• Loop using basement before doing a true loop, prevents loop enemies from spawning.
  
• Take special elevators to skip bosses
  
• Avoid Witch Begon With Fuji
  
• Upgrade Damage then Health
  
• Maximize item potential and avoid bad items (Dead Eye, Chaos Token, Pea Shooter, etc)
  
• Avoid Toilet Paper unless you have wet wipes or a bathroom elevator with a clear path and a medkit.

While this run is essentially chaos your general game knowledge you should have to even attempt this run should be more than efficient.

Facing Chunks is going to happen whether you like it or not and he will not be ignored.
He spawns extremely quickly so the best thing to do is to knock him out first thing every floor.

IF YOU HAVE ACTIVATED A PORTRAIT DEMON DO NOT LEAVE THE ROOM face and knock out Chunks then deal with the demon in the next room. If you fail to do this may Gabe Newell help you.

Chunks will mutate after the first floor, be especially careful of the dog mutation (tips and tricks on Chunks provided below).

Getting the dead rat will resolve any Chunks issue permanently but you should never count getting it in a run. Chunks will also be gone in the dream floors.

Regular Chunks:

• Attack as he slowly walks towards you. When he raises his fist back up and jump to avoid damage.
  
• When Chunks jumps he will land with a sound wave attack. Jump over it to avoid it.
  
• Easiest Chunks to deal with just be careful.

Tentacles Chunks:

• Will approach you quickly to attack.
  
• Can open his head to spew tentacles out in every direction, dodge by getting in between the tentacles, and feel free to attack him.
  
• Can put his hand in the ground and shoot tentacles from it, an X will appear on the spots that the attack will come from. Great time to attack.

Dog Chunks:

• Will originally approach you slowly, best time to attack while you can.
  
• Has a chase attack that will run after you for a set time before hitting a wall causing debris to fall. Chunks is stunned fro a short time after this so take advantage of this.
  
• Will pound on the floor creating multiple shock waves to damage you. Jump over them and attack if you can.

Special Tips:

• Fuji's high damage is great here just be careful to dodge, reading Chunks attacks are crucial.
  
• As Boss be careful of knocking Chunks towards you with explosives via a missed shoot that hits the wall.
  
• As Axel keep the pressure on and use the ice hatchets to keep Chunks stunned.

More of a nuisance than anything. Will be activated by being too close to it's painting and spawn after you move to the next room. LISTEN FOR THE JINGLE

Despawns after two minutes, going into a boss room with the boss STILL ALIVE, getting hit by it, or leaving the floor. Note: Invincibility items do work against the demon and will despawn it despite no damage being done.

Getting hit by the demon is a run killer (REDUCES YOU TO 1HP and it spawns often. Using the free ambrosia for these moments.

Only a problem on the main floors, during the dream floors the demon also slumbers.

Exploit: Apparently if you enter the shop at just the right time (moments before the demon hits you) you can wait out the demon without getting damaged. (Credits to buggle for pointing out this exploit)

I still advise moving between rooms and maneuvering around the demon over this exploit since you can't be sure that you did it right nor will you have a shop that can help you already found.

Remember all floors are mixed up meaning any enemy can spawn!

• Normal Floors 1-4 will be mixed
  
• Alt Floors 1-4 will be mixed
  
• Dream Floors will be mixed

Only real solution is to buy the map at Cordelia's Shop. Avoid Globe it won't help you and instead only hinder you.

Try to get the item X Marks the Spot since every normal room is secret due to curses every room is reveled. Does not show shops and Treasure and Chest rooms are also secret.

Search the edges for the shops first to find the map.

When you have the map try to remember where you are manually since the game will not show it, you should be centered in the middle of the map. Map will not track where you have been.

As many times you feel comfortable, you should at least loop once for getting the bed setup but this will not guarantee you are ready.

Keep looping until you have high health (I had 60 as Fuji) and damage (Fuji's punches did 106 damage).

Always loop with basement by going to Floor 1

Don't forget you have a little bit of time to upgrade in the dream levels but once you enter the dream levels no special floors/elevators will spawn.

These are a bit general and obvious but better safe than sorry.

• Have high health, the more the better.
  
• High Damage is a must, the boss has high health for each phase.
  
• Invincibility items are your best friend

First Phase:
Jump and hit, the boss is extremely mobile and can not be stopped. Do what damage you can.
All of the attacks are highly telegraphed so you should be able to dodge most of them.

Second Phase:
Way easier to hit, but attacks are barely telegraphed so be on the look out. Try to get this one done as soon as possible.

Boss Rush Phase:
All Bosses are at low health take advantage of that and go at them. They should be easily killed in one hit.

Final Phase:
Don't wait for the special credits roll, attack as soon as possible and aim for the head aim for the body since it will do more damage overall and has a shared health pool with the head which will show the true health of the boss if you have the Stethoscope item (credit to Anonymo Stilton). After dealing the final blow the challenge is complete.

This list is not exhaustive, use your own judgement

• Stethoscope
  
• Heart Of Ice
  
• Invincibility Armor
  
• Medkit
  
• Tax Form
  
• Any No Downside Damage Buff
  
• Any No Downside Health Buff
  
• Toy Chest #1 - Item will rotate between three options
  
• Glory Box