All About My Mother is about a film about a nurse involved with donor organ transplants and a single mother who lost her son in an accident. Esteban, a teenager who aspired to become a writer is killed when a car hit him during an attempt to encounter an actress for her autograph after a performance of " A Streetcar Named Desire." The actress portrayed Blance DuBois.
A nurse named Manuela works with colleagues on a man in need of a heart transplant. The heart used for the procedure was donated by her son Esteban after his death. Manuela leaves her job and travels to Barcelona in search of Esteban's father. Her son's father turns out to be a transvestite named Lola. Esteban never knew about it. At the same time, Lola is unaware of the son that they once had.
Manuela meets with Agrado, a transsexual who works as a prostitute. Manuela meets with many others including a nun named Rosa, who is pregnant with a child fathered by Lola. She also befriends Rosa's mother, Huma Rojo, the actress who Esteban attempted to encounter, and a drug addict named Nina. Manuela works as a caretaker for Rosa and also as an assistant to Huma. Nina, also an actress takes in Manuela as her understudy. On the way to the hospital for Rosa to deliver her baby, Manuela and Rosa encounter the latter's Alzheimer's stricken father. Rosa's father does not recognize his own daughter. Later, Rosa dies while giving birth to her child.
At Rosa's funeral, Lola and Manuela meet again, only for Lola to reveal that she is suffering from AIDS. Manuela informs Lola about their son and mentions Esteban's death. Manuela adopts Rosa's child and names it after Esteban. Manuela takes Esteban back to Madrid without saying goodbye to her friends. Two years later, she returns to live with Esteban's grandparents.