On use, the character, including stats and initial items, is reset and teleported to a unique Bedroom that acts like an I AM ERROR room. It has a Bed, two random Chests, two Sacks, and a random Trinket. The only way out is through the trap door.
For every item removed using Genesis, there will be a set of three items from the removed item's pool to choose from, each set appearing one after the other.
If used as Jacob and Esau, both the characters will get all their items removed, but you'll be only presented with replacement pedestals for items removed from the character using Genesis, likely resulting in a net item loss.
If you are or willing to go on the alternate path, the trapdoor can deviate you from this path.
In Challenges, using this item will restore you to your original loadout, but with duplicates of your Passive items. This is specifically because your starting items in Challenges are hardcoded to not be rerolled or removed.
Bug!
If Isaac had multiple copies of any given item before using Genesis, many more sets of items will be presented than normal.
Bug!
Using Genesis as Jacob and Esau causes the link between characters to break - Esau can die without killing Jacob, and speed does not get synced between them.
Bug!
Using Genesis as Tainted Forgotten causes the link between characters to break - Tainted Soul will now die in a single hit regardless of health remaining. Quit and continue repair the link and repair the health issue, but objects taken before will be stuck on tainted soul and unusable.
Bug!
After using this item in the run, the trapdoor on womb to sheol will lead to cathedral.
One time use
Bug!
Jacob and Esau Unlocks 
The Binding of Isaac: Rebirth 
Achievements
Attributes
Bosses
Cards and Runes
Challenges
Chapters
Characters
Co-op
Items
Item pools
Monsters
Objects
Pickups
Pills
Rooms
Seeds
Transformations
Trinkets
