Having once again bested casino owner Terry Benedict (ANDY GARCIA), Danny Ocean (GEORGE CLOONEY) and his team of criminals have gone their separate ways. Yet, when ruthless businessman and casino boss Willy Bank (AL PACINO) double-crosses former casino owner and Ocean team player Reuben Tishkoff (ELLIOT GOULD) and leaves him unconscious from a myocardial infarction, Danny and right-hand man Rusty Ryan (BRAD PITT) reassemble their team to get revenge on Bank.
As the two consult with tech expert Roman Nagel (EDDIE IZZARD), the rest of the players arrive, including Basher Tarr (DON CHEADLE) who works with an expensive tunneling device that's to be used as a diversion. As Livingston Dell (EDDIE JEMISON) works on the card dealing machines and Frank Catton (BERNIE MAC) sets up shop as a dealer, brothers Virgil (CASEY AFFLECK) and Turk (SCOTT CAAN) end up getting involved in a Mexican labor dispute where they're working undercover to fix dice that will eventually make their way into the plan.
Meanwhile, Linus Caldwell (MATT DAMON) acts like the personal assistant to Yen (SHAOBO QIN) who's posing as an ultra-wealthy gambler, all to get closer to Bank's personal assistant Abigail Sponder (ELLEN BARKIN). And Saul Bloom (CARL REINER) dons a disguise again, this time to convince Bank that he's possibly the covert reviewer assigned to rate the new casino, all while that real man -- self-labeled as The V.U.P. (DAVID PAYMER) or very unimportant person, repeatedly gets abused from a hotel service perspective by various members and ploys of Ocean's team.
With them forging an unlikely alliance with Benedict for some much-needed operational funds, the criminals and con men set out to ruin Banks on the opening night of his upscale casino.