Two months after obtaining the key to the Entity’s source code, IMF agents Ethan Hunt and Grace confront Gabriel, its former proxy. Gabriel reveals the Entity has abandoned him and coerces Ethan into retrieving the core module—revealed as the "Rabbit's Foot"—from the sunken Russian submarine Sevastopol. Ethan, Grace, and their team, including Benji Dunn, former lieutenant Paris, and CIA agent Theo Degas, work to stop Gabriel, who seeks to gain control over the Entity.

Luther Stickell sacrifices himself to disarm a nuclear bomb in London, revealing Gabriel stole a malware-loaded hard drive—the "Poison Pill"—meant to trap the Entity. With nuclear apocalypse imminent, Ethan convinces President Sloane to let him act independently. His team locates William Donloe on St. Matthew Island, who provides the Sevastopol’s coordinates. Ethan dives, retrieves the module, nearly drowns, but is revived.

The team heads to a South African bunker, but Gabriel, Kittridge, and others converge. Gabriel activates another bomb and flees. Paris helps save Benji, and Donloe prevents disaster by detonating early. As the Entity prepares to relocate and seize global nuclear systems, Ethan chases and kills Gabriel mid-air. He escapes with the Poison Pill, enabling Grace to trap the Entity just before launch.

Kittridge is frustrated by Ethan’s destruction of the module, but CIA superior Jasper Briggs—secretly Jim Phelps Jr.—reconciles with Ethan. The IMF team reunites in London, Grace hands Ethan the drive containing the Entity, and the team parts ways.