Make the game ridiculously easy.
Early Hell and Hyperium Mask
Hyperium Mask is broken in v1.1.3 (2023-07-11), gives +40 DEF, making you a tank in the midgame.
All you need to craft it is hyperium, the mineral deposit in Hell region.
To get into Hell, however, you need to pass the demon challenge, which requires a high health and/or DEF to survive the punishment.
Luckily, there is just the way – equip the Blood Exchange and Fortified Soul badges. This should give you just enough survivability to pass the challenge and get into Hell much earlier than intended. Then, seek rooms you can win and farm up hyperium to be able to craft Hyperium Mask.
Lategame Flare Vortex
Chains are the best weapons in the game and Flare Vortex is the best chain weapon.
Equip the Tornado Chain and Colossal Strength badges, hold own attack forever and mindlessly own everything. I had to switch to a ranged weapon only for Old King’s 3rd phase.