Starting the game with only one heart container. This means that without acquiring additional heart containers, soul hearts, or black hearts, doing any self-damage will instantly kill Judas.
However, with the ability to access all Secret Rooms, Super Secret Rooms, and Crawl Spaces on all floors, as well as free access to all the pickups that tinted rocks, urns, mushrooms, skulls, and polyps provide, experienced players can get very easy runs.
Strange Attractor is highly effective, because most enemies and some bosses will be pulled towards the missiles instead of targeting the player. However, finding it is extremely unlikely because it is only found in the Treasure Room item pool.
Destroying all rocks and destructible objects on every floor, as well as accessing both Secret Rooms on each floor, is a vital aspect to completing the challenge easily.
Loki's Horns are difficult to utilize effectively with Epic Fetus. However, the extra crosshairs can move through walls and are always the same distance from the character as the main crosshair, so pretend that they are not there, and just avoid taking damage from the main crosshair.
Brimstone will make this challenge incredibly easy. It synergizes with Epic Fetus, firing 10 blood lasers. If Loki's horns activate, the 40 lasers will usually cover an entire standard size room. With 20/20 or the Bookworm transformation, the 80 lasers will destroy most bosses in one shot
Spirit Sword overrides Epic Fetus, arguably making the challenge easier by removing any chance of self harm or need to aim Epic Fetus missiles.