Scientist Bruce Banner is the adopted and emotionally repressed son of Dr. David Banner, a genetics researcher who exposed himself to gamma radiation and accidentally passed on altered DNA to his son. Bruce works alongside his ex-girlfriend, brilliant cellular biologist Betty Ross, at Berkeley in California. They are researching nanomed technology to unleash the human potential for regeneration and rapid healing. Following an accident in the lab where Bruce is exposed to a high dose of gamma radiation, he miraculously survives without any apparent harm. However, the incident triggers something deep within him, something genetically implanted by his father's experiments.

Unbeknownst to Bruce, the exposure has awakened an inner beast—a monstrous alter ego fueled by rage. Every time he gets angry, he transforms into a massive green creature of immense power, which the military, led by Betty's father, General Ross, quickly becomes interested in. Meanwhile, David Banner resurfaces with objectives of his own, fueled by a twisted obsession with his past research and his son's new abilities. As Bruce grapples with the truth about his father and the source of his own inner fury, he must contend with both the military's efforts to capture him and the monstrous enemies spawned by his father's dangerous experiments, all while struggling to control the powerful force within that seeks release through his anger.