The story begins as a group of characters wash up in a shore of a deserted island. The group of people have no idea what awaits and are unaware about the disappearance of all the inhabitants of the island twenty-nine years ago. However, they are not alone, as the Shibito (living dead) are everywhere.
The player takes control of a pair of unfortunate people, Mamoru Itsuki and a young girl named Kishida. To survive the playes can either use stealth and cunningness, resort to using variety of weapons against the Yamibito (people of the dark) and the Shibito.
Forbidden Siren 2 features an enhanced Siren sight-jacking, which allows players to see through the eyes of animals and through the eyes of the Shibito and the Yamibito.