While in pursuit of cop Johnathan Graves, his demonic nemesis, Faust, sends his disciple Alexandria to hunt down the amulet that will set him free. Meanwhile, the Ghoulies find their way through an open porthole and onto the streets of L.A., creating madness and mayhem as they search for a way to get back home. As the body count rises, it becomes an ultimate battle between a demonic killer, a rule-breaking cop, and our favorite creatures from the netherworld!

When vengeful General Francis X. Hummel seizes control of Alcatraz Island and threatens to launch missiles loaded with deadly chemical weapons into San Francisco, only a young FBI chemical weapons expert and notorious Federal prisoner have the skills to penetrate the impregnable island fortress and take him down.