Mission: Impossible III/Best scene/Tom Cruise/Jonathan Rhys Meyers/Philip Seymour Hoffman/Maggie Q

Six years after the events of the previous film, Ethan Hunt has retired from field work for the IMF. He instead trains new recruits while settling down with his fiancée, Julia Meade, a nurse who is unaware of Ethan's true job. He is approached by fellow IMF agent John Musgrave about a mission to rescue one of Ethan's protégés, Lindsey Farris. Lindsey was captured while investigating arms dealer Owen Davian. Musgrave has already prepared a team for Ethan: Declan Gormley, Zhen Lei, and his old partner Luther Stickell.

The team rescues Lindsey and collects two damaged laptop computers. As they flee, Ethan discovers an explosive pellet implanted in Lindsey's head. Before he can disable it, it goes off and kills her. Back in the U.S., Ethan and Musgrave are reprimanded by IMF Director Theodore Brassel. Ethan learns that Lindsey mailed him a postcard before her capture and discovers a magnetic microdot under the stamp.

IMF technician Benji Dunn recovers enough data from the laptops to determine Davian will be in Vatican City to obtain a mysterious object codenamed the "Rabbit's Foot". Ethan plans a mission to capture Davian without seeking official approval. Before leaving, he and Julia have an impromptu wedding at the hospital's chapel. The team successfully infiltrates Vatican City and captures Davian.

On the flight back to the U.S., Ethan threatens to drop Davian from the plane as he interrogates him about the Rabbit's Foot, but Davian refuses to reveal anything. After landing, Ethan learns that the microdot contains a video of Lindsey warning that Brassel is seemingly working with Davian. The convoy taking Davian across the Chesapeake Bay Bridge–Tunnel is attacked by German-speaking mercenaries deploying a UAV drone who have been hired to locate and extract Davian from IMF custody, and Davian escapes. Realizing Julia is also in danger, Ethan races to Julia's workplace, only to discover she has already been kidnapped. Davian calls Ethan and gives him 48 hours to recover the Rabbit's Foot in exchange for Julia's life. But before Ethan can do anything, he is captured by the IMF.

Musgrave takes part in Ethan's interrogation but discreetly mouths that the Rabbit's Foot is located in Shanghai, China, and provides Ethan with the means to escape. Ethan successfully escapes IMF headquarters shortly thereafter, resulting in him being declared an enemy of the state and placed on Interpol's most wanted list.

Ethan then secretly travels to Shanghai where Declan, Zhen, and Luther, sent by Musgrave under the guise of another operation, assist him in acquiring the Rabbit's Foot. As he delivers the Rabbit's Foot to the meeting point, Ethan is tranquilized. When he comes to, a micro-explosive is implanted in his head. The restrained Ethan sees Davian holding Julia at gunpoint, gagged to a chair. Despite Ethan asserting that he brought the real Rabbit's Foot, Davian shoots Julia and leaves. Musgrave arrives, and reveals himself as the IMF traitor; he explains that Julia is still alive, and the woman killed was not Julia, but Davian's head of security disguised as Julia, executed for failing to protect him in Vatican City. The ruse was to confirm the authenticity of the Rabbit's Foot. He arranged for Davian to acquire the Rabbit's Foot and sell it to a terrorist group so that IMF would have reason to launch a preemptive strike.

When Musgrave lets his guard down, Ethan manages to knock him unconscious. He frees himself and uses Musgrave's phone to track the last call's location to find Julia. With help from Benji on the phone, he locates the place, but encounters Davian and some of his henchmen. Ethan kills the henchmen, but Davian triggers the explosive in Ethan's head. Ethan fights him and manages to kill him. He comes back to free Julia, and then jury-rigs an impromptu defibrillator to deactivate the explosive. Julia fights off and kills a henchman, then Musgrave, who is carrying the Rabbit's Foot. She successfully resuscitates Ethan, who explains his true IMF career to her.

Back in the US, Brassel and others congratulate Ethan as he leaves for his honeymoon with Julia.