Kumail, a Pakistani-American comedian, meets Emily, a white graduate student, after one of his stand-up sets. Their connection quickly grows into a romantic relationship, despite their initial reluctance to become serious. However, cultural pressures from Kumail’s traditional Muslim family, who continually set him up with potential Pakistani brides, create strain and lead to their break-up. Emily is devastated by Kumail's inability to confront his family's expectations and prioritize their relationship.

Shortly after their break-up, Emily falls extremely ill and is placed in a medically induced coma. Kumail, despite their recent split, finds himself drawn back to her side out of concern and lingering affection. He meets Emily's parents, Beth and Terry, who initially struggle with him being there due to the circumstances of their break-up. As Emily's condition remains dire, Kumail forms an unusual bond with her parents while navigating the complexities of his own family's expectations and grappling with his true feelings for Emily.