Five years after the events of Borderlands, the valuable mineral, Eridium, has appeared across the planet and Handsome Jack has arrived to take over the 'civilized' planet. Claiming responsibility for finding the vault, Jack has ruled Pandora with a reign of terror, side-lining the original vault hunters.

In Borderlands 2, players take on the role as one of four new vault hunters, this time looking for both a new, greater vault, and the end of Handsome Jack's tyranny, with the help of allies both old and new.