Four years after the original demonic possession of young Regan MacNeil, she is now under psychological care to help her cope with memories of the traumatic events. Dr. Gene Tuskin employs a psychiatric device to study her, believing science can unravel the mysteries behind her experience. Meanwhile, Father Philip Lamont is commissioned by the church to investigate the death of Father Merrin, who died performing Regan’s exorcism. Lamont soon experiences strange occurrences that lead him to believe the demonic forces are not entirely gone. He delves into the origin and nature of the demonic entity known as Pazuzu, seeking answers that blend faith and science, all while Regan reveals unexplained abilities suggesting the demon’s influence might still linger.

Father Lamont's investigation takes him across continents, from modern American cityscapes to the mysterious highlands of Africa, where he uncovers a history of possession linked to a healer named Kokumo. The priest's journey intertwines with Regan’s continued therapy sessions, revealing a deeper, more complex connection between them all and the forces they face. As Lamont battles his own doubts and fears, he faces a series of harrowing encounters that bring him closer to the truth but also drive him further into danger. The story weaves a tense and mysterious atmosphere as science and spirituality clash, leading to an ultimate confrontation whose outcome could determine the fate of Regan’s soul and perhaps the world itself, leaving the audience questioning the nature of good and evil.