After narrowly avoiding a catastrophic encounter with a colossal Gauna that left many human lives lost, Kobayashi, captain of the Sidonia spaceship, rethinks her political beliefs. Her new objective is to eliminate all Gaunas in the Lem system, where former Sidonians have established a colony. Two breakthroughs have boosted her aspiration: the development of superior long-range anti-Gauna weapons and the human-Gauna hybrid, Tsumugi Shiraui, who has immense destructive power. Despite the resistance against chimeras and the uncertain nature of a large-scale military operation, Kobayashi solicits the help of Nagate Tanikaze. Tanikaze, a new elite pilot with personal experience of Shizuka Hoshijiro and Benisuzume's placenta, swiftly develops a close relationship with Tsumugi. As humanity's most ominous adversary draws near, Tanikaze cherishes the last moments of tranquility with Izana Shinatose. Meanwhile, Kobayashi covertly pursues an experimental weapon that could potentially result in the eradication of the Sidonia.