Seven years after the events in the first film, Luc Devereaux (Van Damme), now an ordinary human, is a technical expert who is working with the government with his partner Maggie (Kiana Tom), who has been through countless hours of combat training with him, in order to refine and perfect the UniSol program in an effort to make a new, stronger breed of soldier that is more sophisticated, intelligent, to spare using living soldiers in the battlefield. All of the new UniSols, which are faster and stronger than the original UniSols, are connected through an artificially intelligent computer system called S.E.T.H. (voice of Michael Jai White), a Self-Evolving Thought Helix. When S.E.T.H. discovers that the Universal Soldier program is scheduled to be shut down because of budget cuts, it takes matters upon itself to protect its life. Killing those who try to shut off his power, and unleashing his platoon of super soldiers, led by the musclebound Romeo (Bill Goldberg), S.E.T.H. spares Devereaux, only because Devereaux has the secret code that is needed to deactivate a built-in program that will shut S.E.T.H. down in a matter of hours. With the help of Squid (Brent Hinkley), a rogue cyberpunk, S.E.T.H. is able to put his program in a UniSol which Squid made superior to any of the newer models (White).