"Chrome Shelled Regios" is set in a post-apocalyptic world where humanity survives in mobile cities called Regios, constantly on the move to evade monstrous creatures known as Filth Monsters. These cities are powered by advanced technology and protected by Military Artists, individuals trained to wield Kei, a form of energy that enhances physical and combat abilities. The story primarily unfolds in the academic city of Zuellni, where students train to become Military Artists while balancing their studies and personal lives.

The protagonist, Layfon Alseif, is a former elite Military Artist from the city of Glendan. Seeking a quieter life, he enrolls in Zuellni under the alias "Fon Fon" to escape his past. However, his exceptional skills quickly draw attention, and he is reluctantly recruited into the 17th Military Arts Platoon, led by Nina Antalk. Nina, a determined and ambitious leader, strives to strengthen her platoon to protect Zuellni and prove its worth among other cities. Layfon's involvement with the platoon forces him to confront his past and the responsibilities he tried to leave behind.

As the series progresses, Layfon's relationships with his teammates deepen, particularly with Nina and Leerin Marfes, his childhood friend who harbors feelings for him. Leerin, who resides in Glendan, communicates with Layfon through letters, providing a connection to his former life. Meanwhile, the platoon faces various challenges, including battles against Filth Monsters, internal conflicts within Zuellni, and the mysterious activities of the Heaven's Blade successors, elite warriors from Glendan.

The narrative explores themes of identity, duty, and the consequences of power. Layfon's struggle to reconcile his desire for a peaceful life with his innate talent for combat forms a central conflict. The series also delves into the broader societal structure of the Regios, the origins of the Filth Monsters, and the enigmatic role of the Electronic Fairies, sentient beings that govern the cities. As secrets about the world's history and Layfon's own past are revealed, the stakes escalate, culminating in a climactic confrontation that tests the resolve of the characters and the future of humanity.