Gameplay in The Pre-Sequel is similar to Borderlands 2, but with the addition of new mechanics. Two varieties of items have been added, including laser guns, and items possessing a cryogenic elemental effect, which can be used to slow down and freeze enemies. Enemies that are frozen take increased damage from explosive, melee or critical attacks and are smashed into pieces when killed. The game features low-gravity environments, causing players to jump higher but slower, and items such as loot and dead bodies to float away. O2 kits are added to supply air while in space; oxygen supplies can be replenished using generators, vents, and through oxygen tank items dropped by enemies. The kits can be used like a jetpack to perform double jumps, hovering, and ground slamming attacks; as with other items, different types of O2 kits can provide stat bonuses and affect how ground slams deal damage. A new "Grinder" machine allows players to deposit combinations of existing weapons to receive one of higher rarity.  Vehicles were introduced, including a Moon buggy, and the "Stingray"—a type of hoverbike. 
As with Borderlands 2, completing the main campaign with a character unlocks "True Vault Hunter Mode", a second playthrough that is higher in difficulty, while beating the mode and reaching level 50 unlocks the third playthrough "Ultimate Vault Hunter Mode