Quote, Curly, and Balrog have spent a long year enjoying their new lives away from the island after the events of Cave Story, and the defeat of The Doctor and Ballos. Suddenly, and without warning, they are teleported back to the island by a desperate and defeated Jenka, and immediately separated. From the get-go it's evident that the entire island has been physically changed by some strange forces acting upon it. What has happened to the island after the previous events? It's up to Quote to find his friends and figure out the mystery behind these new forces, meeting old allies and new enemies along the way.