"Megalobox" is set in a dystopian future where society is sharply divided between the wealthy elite and the impoverished underclass. The story centers on Junk Dog, an underground fighter who participates in rigged matches using Gear, mechanical exoskeletons that enhance physical combat. Despite his talent, Junk Dog struggles with his identity and purpose, living in the slums and working under his coach, Gansaku Nanbu, who orchestrates the fixed fights.

The narrative takes a decisive turn when Junk Dog encounters Yuri, the reigning champion of Megalonia, a prestigious boxing tournament where fighters compete with Gear. Inspired by Yuri's skill and driven by a desire to prove his worth, Junk Dog adopts the alias "Joe" and enters the tournament without Gear, relying solely on his raw strength and determination. This decision sets him on a path to challenge not only the physical limits of his body but also the societal structures that oppress him.

Throughout the series, Joe faces a series of formidable opponents, each representing different facets of the world's inequality and corruption. His journey is marked by personal growth, as he confronts his past, builds relationships with those around him, and grapples with the moral complexities of his choices. Key characters include Nanbu, whose shady dealings and paternal instincts create a complex dynamic with Joe, and Sachio, a young boy who becomes Joe's loyal supporter and symbolizes the hope of the marginalized.

The tournament serves as a backdrop for exploring themes of resilience, identity, and the human spirit's capacity to overcome adversity. As Joe progresses through the ranks, his battles become increasingly symbolic, reflecting the broader struggles of the disenfranchised against a system designed to keep them down. The series culminates in a climactic showdown between Joe and Yuri, a confrontation that transcends mere physical combat and becomes a testament to the power of perseverance and self-belief.