Strain occurs after the events of Doom II. A military officer in a secret base on the Earth's moon has been engineering demons, creating a new breed of Hellspawn which breaks free of its confines, making an initial landing on Earth. The Doom marine undergoes an experimental treatment to increase his combat potential. Its side effect is that it leaves virtually all of its subjects in a state of perpetual, murderous aggression. The in-game story follows four episodes as the marine fights to an infested spaceship that has landed on Earth, afterward battling his way deep into the heart of the secret installation where the demons originated from.