The US military receives critical intel that the President of Pakistan has been killed, raising fears that nuclear weapons could fall into the hands of terrorists. In response, the Joes are tasked with securing these dangerous armaments in Pakistan, under the orders of Zartan (Arnold Vosloo](/actor/arnold-vosloo)), who is masquerading as the President of the United States (Jonathan Pryce). The operation appears successful as they manage to secure the nuclear warheads. However, while awaiting extraction at a forward base, a military strike obliterates the entire team, leaving only Roadblock (Dwayne Johnson), Flint (D.J. Cotrona), and Lady Jaye (Adrianne Palicki) alive.
Roadblock speculates that only the President could have ordered such an assault on the Joes. The three survivors stumble upon a remote airfield, and manage to capture a flight back to the US. Upon their return, the POTUS accuses the Joes of assassinating the Pakistani President—an act allegedly carried out by Snake Eyes (Ray Park)—and accuses them of conspiring to steal the nuclear arsenal, branding them as traitors. In light of these accusations, the POTUS convenes with major world powers to discuss nuclear disarmament.
Meanwhile, Storm Shadow (Byung-Hun Lee) and former Joe Firefly (Ray Stevenson) execute a daring rescue of Cobra Commander (Luke Bracey) from an underground maximum-security prison in Germany. An injured Storm Shadow retreats to a Himalayan temple for recovery. Back in the mix, Cobra Commander is overseeing the ominous Project Zeus, which is set to launch in 48 hours.
In an effort to bring Storm Shadow to justice for the murder of his uncle, the Blind Master (RZA) dispatches Snake Eyes and his talented apprentice Jinx (Elodie Yung), who is also Storm Shadow's cousin, to locate him. The Blind Master advises Jinx to find her inner peace if she aspires to become a formidable warrior.
After regrouping in the US, Roadblock, Flint, and Lady Jaye establish a new base of operations in a dilapidated gym. When Zartan announces that Cobra will replace the Joes as the country's main defense force, Lady Jaye suspects something amiss. Through careful analysis of the President's past footage, she discovers disconcerting changes in his mannerisms that signal he may be an imposter.
Determined to uncover the truth, they seek out General Joseph Colton (Bruce Willis](/actor/bruce-willis)), who supplies them with weapons and aids their infiltration of a fundraiser where the fake POTUS will make an appearance. Lady Jaye manages to steal a DNA sample from the President, confirming that it is indeed Zartan. They narrowly evade a confrontation with Firefly and Zandar ([att Gerald), head of the Presidential Detail and affiliated with Cobra.
In parallel, Snake Eyes and Jinx apprehend Storm Shadow at his mountain sanctuary for healing. After an intense battle against loyal ninjas, they transport him to Tokyo, where Storm Shadow defends his innocence regarding his uncle's death by fighting with the weapon associated with the crime, only for it to fail—revealing it is not made of the renowned Arashikage steel. The Blind Master deduces that Zartan is the true murderer of the Hard Master, having framed Storm Shadow to infiltrate Cobra from within. Now exonerated, Storm Shadow joins forces with Snake Eyes and Jinx to combat Cobra and avenge his uncle.
Zartan orchestrates a summit with world leaders, coercing them into disabling their nuclear arsenals. In a catastrophic display, he launches US nuclear warheads, forcing other nations to comply, subsequently self-destructing them, and leaving the world devoid of nuclear weapons. He unveils Project Zeus: seven devastating orbital kinetic bombardment weapons at his command, and demonstrates their potential by obliterating central London, putting other capitals in imminent threat should they resist Cobra.
However, in a shocking twist, Storm Shadow betrays Cobra Commander and eliminates Zartan, exposing the scheme to the global leaders. As chaos unfolds, particularly with Snake Eyes, Jinx, and Flint engaging Cobra's troops, Cobra Commander attempts to initiate the remaining orbital weapons while instructing Firefly to safeguard the launch apparatus.
In a climactic showdown, Roadblock confronts Firefly, culminating in his death, as Roadblock successfully dismantles and destroys the orbital weaponry. Meanwhile, Colton and Lady Jaye rescue the genuine President, resulting in Cobra Commander slipping away during the turmoil while Storm Shadow disappears after avenging his uncle.
In the aftermath, the real President addresses the nation, honoring Roadblock, Lady Jaye, Flint, Jinx, and Snake Eyes as heroes of the day. They are commemorated for their bravery, while Colton salutes them and presents Roadblock with a treasured M1911 pistol previously owned by General George S. Patton. With pride, Roadblock raises the weapon and fires a solitary shot in tribute to his fallen comrades.
