Set far in the future when humanity has left Earth, the plot follows Shion Uzuki, an employee of Vector Industries; and KOS-MOS, a battle android design to fight the hostile alien Gnosis. Forced to escape a Gnosis attack and head for the planet of Second Miltia, Shion and KOS-MOS are pulled into a fight between the Galaxy Federation and the hostile U-TIC Organization. With others who join them as they head to safety, they face a deeper mystery surrounding U-TIC's goals and the plans of the immortal Albedo Piazzolla.