Some time after the events of Tales from the Borderlands, the game's antagonists Troy and Tyreen Calypso learn of other Vaults beyond the planet Pandora, and found a violent cult named the "Children of the Vault" to gain possession of them. Lilith, one of the player characters from the first Borderlands game, recruits the player's new "Vault Hunter" character to help stop the Calypso twins.