Boris Yelnikoff is a misanthropic, middle-aged former professor of quantum mechanics living in New York City. After an unsuccessful suicide attempt, he leaves his wife and meets Melody St. Ann Celestine, a naïve and cheerful young woman who has just arrived from Mississippi. Boris reluctantly allows Melody to stay in his apartment after discovering her homeless plight, and despite his cantankerous personality, they gradually develop an unusual bond. Boris's cynical worldview clashes with Melody's optimistic outlook, but the unlikely pair find a unique equilibrium. As Boris and Melody's relationship deepens, they decide to marry despite their significant age difference and divergent personalities.

Their unconventional marriage faces numerous challenges when Melody's conservative parents track her down. As her mother Marietta arrives, she initially disapproves of Boris but starts to undergo a personal transformation influenced by the bohemian city life. Melody's father, John, also makes his way to New York, leading to further complications. As family dynamics shift and new relationships form, each character reevaluates their beliefs and life choices. The story explores themes of love, chance encounters, and the pursuit of happiness in its many unpredictable forms.