"Spy×Family" is set in a fictional world reminiscent of Cold War-era Europe, where tensions between the nations of Westalis and Ostania are high. The story centers on Twilight, a highly skilled spy from Westalis, who is tasked with a critical mission to prevent war. To infiltrate Ostania’s elite social circles, Twilight must create a fake family to gain access to Donovan Desmond, a reclusive politician whose actions could destabilize the fragile peace. Twilight adopts a young girl named Anya, an orphan with telepathic abilities, and marries Yor Briar, a seemingly ordinary office worker who secretly works as an assassin. Unbeknownst to each other, Twilight, Yor, and Anya all conceal their true identities, creating a dynamic of mutual secrecy and comedic misunderstandings.

Anya, who can read minds, becomes aware of her adoptive parents’ hidden professions but keeps this knowledge to herself, as she is desperate to maintain the family unit she has longed for. Her telepathy often leads to humorous and heartwarming moments, as she navigates the challenges of her new life, including attending an elite academy to help Twilight get closer to Donovan Desmond’s son, Damian. Yor, while initially marrying Twilight as a cover for her own secret life, gradually develops genuine affection for her new family, though her lack of domestic skills and her deadly profession frequently clash with her role as a wife and mother.

The series balances espionage, action, and comedy with themes of family and trust. Twilight’s mission-driven mindset is challenged by his growing attachment to Anya and Yor, forcing him to confront the emotional complexities of his fabricated life. The narrative explores the juxtaposition of their dangerous professions with the mundane yet endearing aspects of family life, creating a unique blend of tension and warmth. The characters’ interactions are driven by their shared need to protect their secrets while inadvertently forming genuine bonds, making "Spy×Family" a compelling exploration of identity, loyalty, and the meaning of family.