The twins suffer complications from their surgery forcing the team at San Jose Boneventure Hospital to make a life-changing decision. Meanwhile, Dr. Shaun Murphy returns to the hospital after his trip with Lea and decides he needs a more permanent change and gives Dr. Aaron Glassman his two weeks' notice.

Dr. Shaun Murphy is surprised to learn that his young cancer patient identifies as a girl while being biologically male. Shaun must quickly learn to understand his patient, her medical needs and how to work with her family, who all feel they know what is best for her.