In the film, Gen and Ryuta Nakaoka join a gang of orphan scavengers and attempt to save their mother Kimie from radiation sickness, a consequence of her survival of the Hiroshima atomic bombing.

While Kimie starts working at a geta factory, Gen and Ryuta attend school in a ruined building, in which they meet a gang of orphaned children and their leader Masa in a hostile first encounter.

Gen and Ryuta start a shoe-shining business that Masa's gang disrupts, drawing the attention of policemen who attempt to place them in an orphanage.

The brothers fight off the police and hide with Masa and their gang in their shelter, where Gen learns that the orphans pickpocket in the black market in order to survive.

Meanwhile, Gen notices that he can now give Kimie piggyback rides despite being much smaller than her, which leads him to suspect that her health is failing.

He and Ryuta learn from doctors that because of the atomic bombing, she is suffering from radiation sickness that progressively worsens with time.

Writer and reporter, Ram Murata (村田らむ（むらた・らむ）) describes their experience watching Barefoot Gen 2 and recalls growing up with the body of work in Japan: "It's a very sad story.