After serving eleven years in prison for the murder of his former nemesis, MacGruber is recruited by General Fasoose for one last suicide mission.
Captured by his mortal enemy, Brigadier Commander Enos Queeth, MacGruber must make an escape or be tortured at the hands of Constantine Bach; Vicki St. Elmo mourns the loss of her former mentor and lover.
MacGruber and the gang race to retrieve the deadly chemical weapon "Brimstone" before the bad guys can get their hands on it.
MacGruber and the gang hatch a daring plan to go undercover at a gala in Miami to stop Queeth from synthesising "Brimstone".
Vicki almost gets "Brimstone" out of the hands of the scientist, Irina Poliskya, but MacGruber gets in the way; a tip from Fasoose sends Mac to Enos Queeth's compound alone for one last chance at revenge.
With the team in shambles, MacGruber attacks Queeth's massive compound to get revenge; Mac needs to use every trick in the book to survive.
The evil plan Queeth set into motion is still alive; MacGruber must find out who is behind the attacks and how to stop them.
With the team back together, all roads lead to the mysterious "Havencroft"; MacGruber, Piper and Vicki fight for survival and to save the world.