Set a year after the events of Band of Thieves, Sly Cooper, Bentley, Murray, and other unidentified characters attempt to open the Cooper Vault on Kaine Island. Unfortunately, they are intercepted by Dr. M, the owner of the island. Murray and Bentley escape, but a monster grabs Sly. During this scene, Sly's life flashes before his eyes, and the game flashes back.
Sly learned that the Cooper Vault was hidden on Kaine Island from one of his father's colleagues, Jim McSweeney. The vault contains the accumulated wealth of the Cooper Clan built up over the centuries. Sly went to find the vault, only to discover that M had built a fortress on the island in an attempt to get at the wealth hidden in the vault. Sly needed additional experts in order to get past Dr. M's extensive security; he needed the Cooper Gang back in action.
First, Sly and Bentley seek Murray, who had left the team due to guilt for causing Bentley's leg injury, which would end up paralyzing him. They learn about a mob boss, Octavio, who operates in Venice, Italy, where Murray was. Sly finds Dimitri in a cell at the local police station. He agrees to find Murray if Sly helps him escape. Sly finds Murray, while evading Carmelita Fox, who had become more hateful towards crimes since their last encounter. Murray had become a trainee for a peace-loving figure known as the Guru in order to become more peaceful. Murray refuses to rejoin Sly and Bentley until the canals are clean, the task the Guru gave to him. Sly and Bentley take down Octavio, who had been polluting the canals with tar as part of a scheme to threaten the city into liking opera again. After putting together some plans, they destroy Octavio's comeback recital, but Octavio injures Bentley, making Murray so mad that he quits his training and battles Octavio and defeats him. Octavio is arrested, and Murray rejoins the team.
