On use, the character, including stats and all items but initial items, is reset and teleported to a unique Clean 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 beam of light.
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 on one of the final floors of the game, such as Chest, Dark Room, or The Void, the beam of light will be replaced with a Crawl Space that leads Isaac back to the starting room of the floor he used it on. In addition, the aforementioned chests will include items. These items will not disappear along the "choice" pedestals. The Mega Satan Door will remain open if it was opened earlier.
If used during The Beast's fight, it will merely teleport Isaac to the middle of the room, removing no items from him.
If used in ???, the beam will teleport Isaac to Cathedral.
Notes[]
Genesis will remove all currently active curses, meaning Curse of the Blind will not affect the item pedestals present inside the room.
Trinkets absorbed using a Gulp! pill or an item such as Smelter will simply be removed with no extra pedestals granted for them.
If used as Jacob and Esau, both character's items are removed to offer choices, but Jacob and Esau cannot take two items at once from the choices.
Tainted Cain will be able to pick up the items that appear normally, one of the few times (aside from plot items and Death Certificate) he is able to do so.
If used as Tainted Lazarus, both form's items are removed to offer choices, while his initial Flip is granted infinite charges and can be used freely in the special room.
If used as Eden, a new set of items and stats will be generated. The first random passive item Eden starts with is rerolled immediately with no choice of three.
If Isaac uses Genesis while in Downpour / Mines / Mausoleum or their variants, the trapdoor can send him back to the regular floors unintentionally.
Using Genesis after defeating Mom's Heart on Mausoleum II will teleport Isaac to a room that is empty besides a trapdoor leading to Corpse I and the three item selections.
Since Genesis resets Isaac's health, it is one way to remove Broken Hearts.
Crawl Spaces can be generated and entered inside the Genesis room, but upon leaving them, Isaac will be returned to the floor Genesis was used on instead of returning to the room.
Similarly, a Red Chest or Joker can teleport Isaac to a Devil Room or Angel Room, and leaving will return Isaac to the room Genesis was used in.
Item tables will not be reset, however any lost items can be obtained again if they spawn.
Take caution; choosing an active item while holding another one will not drop the previous item to the ground, but replace it.
Using Genesis in Womb II / Utero II will only grant access to Cathedral.
If the player acquires Damocles and uses it before all items have been collected, then each subsequent item spawned after using it will each spawn an extra item. Unlike the Genesis choices, the other extra items will not disappear upon collecting one of them, potentially allowing the player to obtain a much higher amount of items than usual.
Synergies[]
Book of Virtues: Replaces all of Isaac's wisps with 3 normal wisps, in addition to its other effects.
Interactions[]
? Card: If ? Card is used in place of Genesis, Genesis will be counted as an extra item for the choice set.
Azazel / Tainted Azazel: Both have the ability to return to the floor Genesis was used on, due to them starting with a 0 - The Fool card.
Crooked Penny: Using it on the choice pedestals has the 50/50 chance of duplicating them as normal, or make them disappear, in which case no new ones will spawn.
D7: Using it will spawn three items, all of which can be taken.
Echo Chamber: The consumable pool is reset when Genesis is used, so if it's re-obtained after using Genesis, the previously stored consumable types won't be activated.
Eden's Blessing: Using Genesis after collecting the blessing during the run will spawn Isaac in the Genesis room already holding a random item. This consumes Eden's Blessing, and the next run Isaac starts will not begin with a random item.
Esau Jr.: Using Genesis as Esau Jr. will revert back to the original character.
Glowing Hour Glass: Using it works as intended and will give back all previous stats, items, pickups, and health.
Magic Skin: Genesis does not remove the downside of Magic Skin; any of the choice pedestals can be replaced by Magic Skin.
Pandora's Box: Using it inside the Genesis room will spawn The Bible. Picking it up does not affect the choice pedestals.
In the case of pills, unidentified pills should only be popped after taking all of the items, for the Genesis room cannot be returned to after leaving.
Genesis refers to the first book in the Bible, and is an Ancient Greek term for "birth". The item description refers to the very first words in the Book of Genesis.
Bugs[]
Bug!
Using Genesis immediately after taking Dad's Note will teleport Isaac to the Genesis room, then to the start of the ascent with no items except those that cannot be removed (Dad's Note, Key Pieces, etc.).
Clean Bedroom that acts like an 
Bug!
Dad's Note will teleport Isaac to the Genesis room, then to the start of the ascent with no items except those that cannot be removed (Dad's Note, Key Pieces, etc.).
Jacob and Esau Unlocks 
Ultra Greedier Unlocks 
