Puffer and Clarissa is an action/adventure story about two girls that takes place on a world that is covered in water, with everyone living on ships and submarines. Planet Aqua is a post-apocalyptic world, but one where technology and magic are advanced enough for humans to continue living. Violence and piracy are not uncommon as some people fight to control others and gain resources. In spite of this, familiar values such as community, love and generosity also find ways to exist. Our 15-year-old protagonist Puffer may be in need of these.

Puffer was raised by her mother, the genius inventor Sharon, to be an obedient servant in her goal of world domination. To achieve this goal and build up her robot army, Sharon often raids and occupies various ship settlements with her daughter. During one routine raid, things change when Puffer gets washed overboard along with another passenger her age, Clarissa.

Since Puffer's mom was raiding Clarissa's ship town, Clarissa has no reason to like Puffer, and the sentiment is returned. But with the girls abandoned at sea and surrounded by sea monsters, ruins, and pirates, they have no choice but to rely on each other in order to make it back home. But does the end of their adventure mean an end to their conflict?