CIA Agent Jane Marke tracks down former xXx operative Xander Cage, who faked his death[a], and has been living in self-imposed exile in the Dominican Republic. She convinces him to return to active service to retrieve the device. In London, after enlisting his old friend Ainsley for help, Xander tracks down the attackers to the Philippines. At an RAF outpost in Lakenheath, a unit of Special Forces operatives led by Paul Donovan is assigned to help Xander, but he rejects them in favor of his own team, composed of sharpshooter Adele Wolff, DJ Harvard “Nicks” Zhou, and getaway driver Tennyson “The Torch”. They are also aided by introverted weapons specialist Becky Clearidge.

The team locates Xiang and his teammates Serena, Talon and Hawk, and Xander meets Xiang in an underground nightclub on a remote island, where Xiang reveals that his team are also xXx agents, recruited by Gibbons. He claims to have stolen Pandora’s Box to prevent its misuse, although Serena believes they should destroy it. Shortly after, Russian soldiers raid the island. The group fends off the attackers, while Xiang escapes with Pandora’s Box. Xander intercepts him chasing him to a nearby beach. Serena betrays him, destroys the Box, and joins Xander’s team, while Xiang escapes and regroups with Talon and Hawk.

After another satellite crash in the Olympic Stadium in Moscow, Marke determines that the device that Serena destroyed was only a prototype and that both teams have been wasting time, while Xander discovers CIA Director Anderson is involved and has the actual Pandora’s Box in his hands. Xander’s and Xiang’s teams race to reach Anderson first in Detroit, tracking Pandora’s Box’s unique signal, with Xander and Xiang fighting and later protecting each other from Anderson’s men. Xander confronts Anderson, who admits to causing the satellite crash that killed Gibbons before Wolff shoots him dead. Xander reluctantly allows the CIA to arrest Xiang in an attempt to frame him for the Moscow attack, and they secure the box.