This challenge focuses on a high risk, high reward style of play. When low on health, Eve can inflict more damage. As a result, the majority of the challenge will be spent in a near-death state.
Since the player is playing as Eve, Whore of Babylon will activate when having 1 Red Heart or less, rather than 1/2. Since she starts with 2 hearts, the Razor Blade can activate this effect immediately.
Because the Razor Blade inflicts damage, using it will also activate the Dead Bird.
Sacrificial Dagger and Dark Matter can be used together. The fear effect can drive enemies away, allowing Eve to chase and kill them with the dagger.
Making one Devil deal can permanently activate Whore of Babylon. However, this can put Eve in a very dangerous position with only one Red Heart. A Dark Bum can produce Soul Hearts, which can allow Eve to maintain a buffer of health while maintaining the Whore of Babylon's effect.
Since all of the starting items are from the Devil Room pool, Eve has a much higher chance to get some of the stronger items such as Mom's Knife or Brimstone. As such, opening the Devil Room as often as possible should be a priority.
Also, to prevent Angel Rooms from appearing later on in the run, it is advised to take the first Devil Deal encountered.
Killing Delirium will count as completing the challenge.
To unlock the challenge, the save file must have everything used by this challenge unlocked on top of defeating Mom's Heart 11 times. This means one must unlock Eve herself first, and then defeat both Satan and ??? as Eve to unlock both the Razor Blade and Sacrificial Dagger respectively.