During a press conference, America's top nuclear physicist, Dr. Adele Burkhart, is denouncing the military for misleading her to working on a doomsday project. Cobra surprises the security detail and gets away with kidnapping Burkhart. Despite her political stance, she must be rescued her else America's nuclear secrets are pried by Cobra. General Flagg sends in the Joe Team for the mission.
Cobra is headquartered on an island in the Caribbean. The Joes are broken in two groups. Grunt, Stalker, Short-Fuze, Snake-Eyes, Scarlett, Breaker and Flash are the insertion team who must destroy and sabotage much of Cobra's facilities in order to make way for the heavy assault team. The heavy assault team will compose of Hawk, Rock 'n Roll, Clutch, Grand Slam, Steeler and Zap.
Using a JUMP jet pack and some grenades, Stalker makes short work of Cobra's coastal defense. The news reach Cobra Commander quickly but he is unfazed, confident in his army's ability to fend off the Joes. Breaker and Flash rig Cobra's radar to continuously display an all-safe reading. Stalker, Grunt and Short-Fuze bombard the airfield with mortar but this one Cobra was expecting and the Joes don't know they only destroyed dummy planes. Meanwhile, separated from Stalker's team, Scarlett and Snake-Eyes make their way through Cobra's fort and destroy the generators. The Commander remains unfazed and informs the Baroness to carry out the next phase of the plan.
The Joes' main assault group arrive at the island and fight through Cobra's armor. Stalker's team encounter the village on the island and find its residents all killed. Flash is initially broken up and Breaker was about to propose doing the decent thing but Stalker would have none of that, reminding the two the mission comes first. Dr. Burkhart is being transported by Cobra to the airfield. The Cobra escort is taken care of and Stalker flies the doctor to safety. Only, she's not Burkhart, it is actually the Baroness in disguise and she tells him his team is doomed.
Now, Cobra Commander reveals his true plan. He never hoped to extract any information from Burkhart. She was merely a bait to lure the Joe Team into a trap. Snake-Eyes and Scarlett show themselves to the Commander but he holds Burkhart hostage and the two Joes find themselves trapped in the same room as him. Cobra Commander informs them that he and Burkhart will be allowed to escape on the plane and the door has a timer that will unlock and let them go. Burkhart refuses to be a hostage and quickly tells the Joes that the timer is actually a bomb. Enraged, the Commander shoots Burkhart while Scarlett hurls a throwing star to his hand.
After having dealt with the Cobra forces, the other Joes have arrived inside the fort. However, in the ensuing chaos, Cobra Commander and the Baroness both escape. With less than five minutes on the bomb's timer, the Joes secure a helicopter and fly away to safety.