Sly is in search for the Cooper family vault, learning of it after he meets with Jim McSweeny in jail, who was his father's muscle. A majority of the game takes place in flashbacks, where Sly gathers new members for the clan to help him break into the vault. The vault is located on Kaine Island, which has been overrun by Dr. M.
After getting Murray back, as well as The Guru, Penelope, Panda King and Dimitri on the team, they infiltrate the island. However, when he is in front of the vault and about to go inside, he is attacked by Dr. M and about to be killed, when Carmelita inadvertantly saves him. He goes into the vault, only to be followed by Dr. M, who he fights. At the end of the fight, Carmelita interferes and Sly jumps in front of her to take the blast from Dr. M. Due to the blast, he appears to have amnesia and Carmelita lies to him, saying he is her partner, and the two of them go off together.
