Fallen soldiers' bodies are retrieved, they are placed into a secret program in which they are reanimated as superhuman agents and trained to become unquestioning killing machines.
Two rival soldiers who were killed in Vietnam are brought back to life in a top secret military experiment that creates superhuman warriors.
Following the events of the original ''Universal Soldier (1992 film)'', the budget of the program has been cut by the government. However, under the orders of a Director of the Central Intelligence Agency, a gang of mercenaries take control of the new line of Universal Soldier (cyborg) to use them in the diamond smuggling business.
Luc Devereaux (Matt Battaglia) and Veronica Roberts (Chandra West) continue their attempts to expose the Universal Soldier (cyborg) unit. After a hostage situation mistakenly leaves Veronica a fugitive, the two escape the city and go into hiding.
The "universal soldiers" must fight the whole army, when the military's supercomputer S.E.T.H gets out of control.
A group of terrorists led by Commander Topov (Zahari Baharov) kidnap the Prime Minister of Ukraine's son and daughter and hold them hostage, demanding the release of their imprisoned comrades within 72 hours. In addition, they have taken over the crippled Chernobyl Nuclear Power Plant and threaten to detonate it if their demands are not met. It is revealed that among the ranks of the terrorists is an experimental Next-Generation UniSol (NGU) (Andrei Arlovski), who was smuggled in by rogue scientist Dr. Robert Colin (Kerry Shale). U.S. forces join up with the Ukrainian Ground Forces at the plant, but quickly retreat when the NGU slaughters most of them effortlessly. Dr. Richard Porter (Garry Cooper), Dr. Colin's former colleague on the Universal Soldier program, revives four UniSols to take down the NGU, but they are systematically eliminated.
John awakens from a coma to find that his wife and daughter were brutally murdered in a home invasion. With the help of Federal Bureau of Investigation Agent Gorman, the still amnesiac John identifies the perpetrator as former Universal Soldier (UniSol) Luc Deveraux, now a wanted man. Gorman activates sleeper agent Magnus, one of the cloned Next Generation UniSols from ''Regeneration''. Magnus reaches a brothel and kills all the women working there and most of the patrons, all men with exceptional physical resistance. His last adversary, a clone of UniSol Andrew Scott and Deveraux's former nemesis, incapacitates Magnus and injects him with a serum that frees him from government control. Magnus is introduced to a separatist group led by Deveraux and Scott, who are taking in wayward UniSols to turn them against the U.S. government, thus establishing a new order ruled by UniSols.