After the success of the Heart-Throbbing School Trip, a reformed Nagito Komaeda accompanies Makoto Naegi to a meeting at the Future Foundation base to decide the fate of the former Ultimate Despairs. He is reunited with several people, including his former lover Seiko Kimura. But after narrowly evading one Killing Game, Nagito soon finds himself about to participate in another one.

After being suspended from Hope's Peak Academy following the bombing of the school gymnasium, Nagito Komaeda crosses paths with an unintended victim of his perceived hopeful actions: Seiko Kimura, the Ultimate Pharmacist.