Set in 2030–2031, ten years after the events of Software, Wetware focuses on the attempt of an Edgar Allan Poe-obsessed bopper named Berenice to populate Earth with a robot/human hybrid called a meatbop.

Toward this end, she implants an embryo in a human woman living on the Moon (Della Taze, Cobb Anderson's niece) and then frames her for murder to force her to return to Earth.

After only a few days, she gives birth to a boy named Manchile, who has been genetically programmed to carry bopper software in his brain (and in his sperm), and to grow to maturity in a matter of weeks.

Before the assassination, Manchile impregnates several women, the idea being that his similarly accelerated offspring will create a race of meatbops at an exponential rate.

Both of the two main human characters of Software play prominent roles in Wetware: Cobb Anderson, whose robot body was destroyed at the end of the last novel, has his software implanted in a new body so he can help raise Manchile; while Sta-Hi Mooney—now known as Stahn Mooney—is now working as a private detective on the Moon after accidentally killing his wife, and is used as a pawn in various bopper and anti-bopper schemes.