André 1 and Dr. Margaret 13, robots with human consciousness, are employed in the White House in the present times. Learning that the unstable President is planning a nuclear attack, André, programmed as a peaceful, reasonable translator, realizes he needs reprogramming for violent actions so he can combat the Situation Room team. While Dr. Margaret reboots André's CPU, he spends the down-time recalling how he was created and eventually came to participate in the present crisis.
Having been created/built by Dr. Phillip Strauss, an eccentric genius, André is used around the Strauss's home, mechanically and unconsciously performing increasingly sophisticated tasks. Experiences cause the robot to gain a Proustian consciousness, rendering him mentally human-like, though without emotions and animal cravings. While in a metal encasement in the shape of and physical capabilities of a grown man, a childlike Andre undergoes adolescent-like experiences as another child in the family. Eventually, a flawed human, Dr. Strauss goes bankrupt, is divorced and dies of alcoholism.
Seized by the U.S. Bankruptcy Court and taken to court by the Trustee to auction him off as a property asset, André objects and demands legal status as a person. He becomes wealthy by trading in bitcoin and gains independence. He works at CIA as analyst until hired as the White House interpreter. Programmed for honesty, André continually is at odds with the conniving, egotistic, dictatorial President.
André secretly constructs himself a girl-friend and companion, Dr. Margaret 13 who is programmed to be a compassionate physician and assigned as physician in the White House.
André continues to irritate the narcissistic and paranoid President with demands for truth-telling and reasonable policies, learning that he must be careful in his candor with him.
Under pressure from investigations into his past, POTUS, irrationally believing that North Korea and China plan an attack, calls an emergency meeting in the Situation Room and recklessly prepares for a nuclear first-strike.
André speaks out in a futile attempt to offer reasonable arguments, is overpowered and expelled, and nuclear war ensues. It is at this point André concludes that he must act combatively to stop a nuclear war. Although he violently attacks the military staff, he is expelled, and nuclear war begins. He and Margaret take refuge as the catastrophe unfolds.
Surviving worldwide nuclear radiation, they lament the end of human civilization. At Dr. Margaret's insistence, the two droids travel to Birmingham, Alabama in search of an embryo research lab. Discovering viable embryos in cryonic storage, they resolve to keep the embryos alive. They recover other robots and make them their team to save the last vestiges of humanity. In the process they begin a new age of robots as the dominant race on Earth--hence the title, ""André's Reboot""