"Spy×Family" is set in a fictional world resembling 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 tasked with a critical mission: to infiltrate Ostania's elite social circles and gather intelligence on Donovan Desmond, a key political figure threatening peace. To achieve this, Twilight must create a fake family to enroll a child in Eden Academy, a prestigious school attended by Desmond's son.

Twilight adopts Anya, a young girl with telepathic abilities, who was previously an orphan subjected to experiments. Anya, eager for a loving family, agrees to play the role of his daughter. To complete the family, Twilight recruits Yor Briar, a seemingly unassuming office worker who secretly works as an assassin. Yor agrees to the arrangement to maintain her cover and avoid suspicion from her employers. Together, the three form an unconventional family, each hiding their true identities from one another.

The narrative unfolds as Twilight, Anya, and Yor navigate their dual lives, balancing their personal goals with the demands of their fabricated family. Anya, aware of her parents' secrets through her telepathy, strives to help Twilight succeed in his mission while yearning for genuine familial bonds. Yor, despite her lethal profession, grows attached to her new family and seeks to protect them. Twilight, initially focused solely on his mission, gradually develops emotional connections with Anya and Yor, complicating his professional detachment.

The series blends espionage, comedy, and heartfelt moments, exploring themes of trust, identity, and the meaning of family. The characters' interactions are central to the story, as their individual struggles and growing affection for one another drive the plot forward. The mission to get close to Donovan Desmond remains a constant thread, with Anya's academic performance at Eden Academy serving as a key element in maintaining the family's cover. The dynamic between the characters, coupled with the high-stakes espionage backdrop, creates a compelling narrative that balances humor, action, and emotional depth.