The world was infected by "Pollutant" years ago - a world cracked open and generally screwed up. This Pollutant spawns nasty "Pollutant Beasts", but it's also resulted in people gaining special powers. The towns that now litter the world are protected by alchemists and are mobile - these are the "Regios" of the title. The story follows a guy named Lei-Fon Alseif who starts at a new school following the disappearance of his childhood friend and gets recruited into the special 17th Platoon in order to combat Pollutant Beasts.