Set in the 1980s, Alpha follows a 13-year-old girl named Alpha who lives with her single mother in a fictional city inspired by New York. Her life takes a turn when she returns home from school with a tattoo on her arm, leading to social ostracization fueled by rumors of her being infected with a new disease. As the AIDS epidemic unfolds globally, one of her parents falls ill, compelling Alpha to confront themes of loss and mortality.