On , Laurie Strode accidentally kills a paramedic with whom her brother Michael Myers (Halloween) had swapped clothes. A guilt-ridden Laurie becomes an inmate at the Grace Andersen Sanitarium, where the nurses believe her to be catatonic. Instead, she is preparing for Michael's return. Three years later, on October 31, 2001, Laurie, pretending to be heavily medicated, prepares herself for the inevitable confrontation with her brother. Michael breaches the facility and kills two security guards, as he makes his way to Laurie. After a chase, Laurie lures Michael on to the institution's rooftop. Although he falls into her trap, Laurie's fears of again killing the wrong person get the better of her; when she tries to remove his mask, Michael kills Laurie by stabbing her and throwing her off the roof. Michael returns home to his abandoned childhood house.

Laurie Strode confronts her long-time foe, Michael Myers, the masked figure who has haunted her since she narrowly escaped his killing spree on Halloween night four decades ago.

Michael Myers escapes Laurie's trap and tries to reach her, killing people on his way. On the other hand, Laurie finds support in a group of survivors of his previous rampages.