Roberta (Arquette) is a frustrated housewife living in suburban New Jersey and is fascinated by a woman known only by the personals section of a New York newspaper. This fascination reaches a limit when an ad entitled "Desperately Seeking Susan" proposed a meeting in Battery Park between this woman and a man who regularly looking for. Roberta also goes to Battery Park and sees the woman (Madonna) whose life is fascinated by both. In a series of events including mistaken identity, amnesia and other absurdities, Roberta involved in a story to Alice style in Wonderland, motivated by the search for a pair of earrings stolen Egyptians.