Forty years after a Halloween night massacre in Haddonfield, Illinois, the lone survivor of the killing spree, Laurie Strode, is living a life of isolation and vigilance, preparing for the potential escape of the masked murderer, Michael Myers, from his confinement in a mental institution. Haunted by the trauma, Laurie has alienated her daughter, Karen, who struggles with her mother's obsession and has attempted to live a normal life with her own daughter, Allyson. As Haddonfield prepares for another Halloween, two investigative journalists visit Myers in the institution, hoping to understand the silent killer before his imminent transfer to a maximum-security prison.

On the eve of his transfer, Myers escapes when the prison bus crashes, prompting an intense manhunt. The obsessed Laurie, whose warnings have been ignored by the community, takes action to protect herself and her family. Her fears are realized as Myers returns to Haddonfield, leaving a trail of terror in his hunt for new victims. Amidst the chaos of Halloween festivities, Laurie must confront her lifelong nemesis in a final struggle to end the nightmare that has consumed her life, while her estranged daughter Karen and granddaughter Allyson are drawn into the horrifying ordeal as they try to survive the relentless threat.