Laurie Strode has narrowly survived an encounter with the relentless murderer Michael Myers on Halloween night. Immediately following the events of the first encounter, Laurie is taken to Haddonfield Memorial Hospital for treatment of her wounds. Unbeknownst to her and the rest of the staff, Michael has escaped the scene of his previous killings and is continuing his murderous rampage. Michael's obsessions drive him to the hospital, where the staff and patients remain unaware of the impending danger creeping closer.

Meanwhile, Dr. Sam Loomis, the psychiatrist who has been tracking the psychotic killer, is frantically searching the town with the help of the police. Convinced that Michael is still on the hunt for Laurie, Loomis digs deeper into Michael's past, uncovering disturbing details that may explain the killer's motives. As the night unfolds, the hospital becomes a backdrop for a game of cat and mouse, with Laurie and the staff members becoming potential victims of Michael Myers' unrelenting pursuit. The confined corridors of the hospital provide a chilling setting for the terror that unfolds as the unsuspecting survivors fight for their lives against an unstoppable force of evil.