Set eight years after the ending of the film, the game begins in a dream sequence where a man named Bruce Banner transforms into a large and powerful monster dubbed the Hulk and destroys waves of soldiers and tanks sent by the military to attack him. Upon awakening, Bruce Banner is contacted by his old mentor Dr. Crawford who explains that he has developed a cure for the Hulk called the Gamma Orb. Unfortunately, military troops led by the corrupt General John Ryker have raided the lab. Bruce Banner sneaks into the lab and discovers that General Ryker wants to obtain the Gamma Orb. After reaching Dr. Crawford, Bruce allows his old mentor to use the Gamma Orb on him, but Crawford uses it to steal the Hulk’s energy. Crawford touches the Orb and absorbs a part of Bruce Banner’s power transforming himself into a Hulk-like creature called Ravage. Simultaneously, Banner transforms into the Hulk. After a chase of Ravage over rooftops and through sewers with Ryker’s forces in hot pursuit, Hulk finds himself at a dead end where he is ambushed by the vampire Half-Life. Hulk defeats Half-Life who explains that Ravage has taken the orb to Alcatraz but will kill a hostage there if the Hulk is detected.
Bruce infiltrates Alcatraz which has been secretly occupied by the Leader and his private army. Bruce deactivates the Gamma detection device using a security terminal which shows live footage of a Gamma chamber used to mutate the Leader’s henchmen into Gamma-irradiated super soldiers. It also shows the Leader’s psychotic brother Madman taking the hostage Betty Ross to the irradiation chamber after being ordered by a mysterious voice to “dispose” of her when she refuses to further aid them in their schemes. Seeing Betty in distress causes Bruce to transform into the Hulk decimating the research facilities and defeating Madman after disabling the irradiation chamber. Betty tells the Hulk that she has been exposed to the Gamma radiation and must be taken to the military Gamma base. The Hulk takes Betty to the base, but is incapacitated by a force field. Bruce is sedated and strapped to an operating table where General Ryker plans on dissecting him. Betty frees Bruce, who (disguised as a soldier) formulates an antidote, transforming into the Hulk and fighting the military while trying to find and destroy the shield generator. Hulk finds the generator, but is confronted by Flux, a Hulk-like soldier. The Hulk defeats Flux and throws him into the generator, destroying it.