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As long as you have at least some HP, know all the modifiers and your weapons are not terrible, you'll be fine for the floors themselves. The bosses are something else though. You can get completely raped by any boss if it has the right modifiers. Make sure you can reliably flawless all the bosses in normal mode (maybe even do a high curse run or two for practice) and pray to RNGsus.
The floor 4 and floor 5 bosses are a little bit different than the others in that they have set modifiers which appear every time and no random ones. Each of the 4th floor bosses has a unique modifier to it, you'll have to get used to these. Wallmonger is pretty much the hardest of them all in challenge mode and kill pillars is the easiest (imo).
The Dragun fight is ridiculous: It's attack patterns themselves are actually modified and more dangerous. You WILL 100% need blanks for this fight or you will die. There is one particular attack which I don't think is even dodgeable. Blanking the knives is probably not the best idea, just try to kill them instead. This fight is also ALWAYS accompanied by the "High Stress" modifier which lowers your health to half a heart for a few seconds everytime you get hit. So keep your cool. Don't panic when you get hit, it could lead to a quick death. Also completely focus on dodging after taking damage and don't be afraid to immediately use a blank if needed.
That said, luck plays a big role in challenge mode and one or two early HP-ups or boss flawlesses can be game changers for your run.
Good luck, fellow gungeoneer.
Floor 4 bosses are easier than floor 1 at this point.
Nope. It's doable without blanks.
It's dodgeable.
SPOILERS/ADVICE
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In regards to creator of the thread, challenge mode has quite a few outs. Fire/poison immunity in form of flying or immunity items helps a ton since it'll make you not have to worry about constant ground effects.
You'll want to value most beam weapons highly, they aren't affected by most of the modifiers which makes them very solid.
Gun queue with right weapons picked up raises your DPS rather highly rather than messing you up, the worst combo with it is thermal clips of course which you counter with, again, a fire resistance or flying item should you get one. Knocking out modifiers with items helps a great deal, though ofc requires a bit of luck.
Since bullet is immune to blobulin rancher, yeah, he is the easiest to do it with.
Pot shots was created by Satan.
Hammer and missiles can't seem to hit you in the area where there's a small "hallway" between the current door and the room you are in, I sometimes hide there as it despawns the hammer if you do it for a couple of seconds. I assume that one is a bug however, so not something I do constantly.
Dragun is always the same, so I'd say he could be the easiest part of the challenge eventually. Considering his new attacks, you'll likely die the first time, at least. Skulls are countered by a beam weapon, knives are the same deal, but his attacks are a lot faster and the dragon breath bounces back from the wall at you. It's still dodgeable but can be tough. Blanks and damage immortality actives are great here, ofc. As well as armor.
Practice makes perfect.
I agree that because there is no randomness to the floor 4 and 5 bosses, the earlier ones can be harder when you encounter them in combination with annoying modifiers.
When I fought the Dragun, the bouncing fire breath attack didn't seem like it was avoidable but since I only fought him once in challenge mode and him being jammed might have affected the difficulty of the fight too, I'm going to accept your correction since I assume you have more experience with it. That said, what's the strategy to dodging it?