27 years after overcoming the malevolent supernatural entity Pennywise, the former members of the Losers' Club, who have grown up and moved away from Derry, are brought back together by a devastating phone call.

CDC researcher Abby Arcane investigates what seems to be a deadly swamp-born virus in a small town in Louisiana but she soon discovers that the swamp holds mystical and terrifying secrets. When unexplainable and chilling horrors emerge from the murky marsh, no one is safe.

Beatrice Prior and Tobias Eaton venture into the world outside of the fence and are taken into protective custody by a mysterious agency known as the Bureau of Genetic Welfare.