"Futari wa Milky Holmes" is a spin-off of the "Tantei Opera Milky Holmes" series, focusing on a comedic and lighthearted narrative centered around two aspiring detectives, Alice and Sherlock. The story is set in a world where individuals possess special abilities known as "Toys," which grant them unique powers. Alice and Sherlock, despite lacking any significant Toys, dream of becoming great detectives like the legendary Milky Holmes team. Their enthusiasm often leads them into absurd and humorous situations as they attempt to solve trivial cases, often with little success.

The main characters, Alice and Sherlock, are students at Holmes Detective Academy, where they idolize the Milky Holmes team. Alice is cheerful and optimistic, while Sherlock is more serious and analytical, though both share a lack of detective skills. Their adventures frequently involve their classmates and rivals, including the eccentric Nero and the aloof Cordelia, who often mock or challenge their efforts. Despite their incompetence, Alice and Sherlock remain determined, driven by their admiration for the Milky Holmes team and their desire to prove themselves.

The series is episodic, with each episode presenting a new case or challenge for the duo. These cases range from solving minor mysteries to participating in school competitions, often resulting in comedic mishaps. The narrative emphasizes humor and parody, frequently poking fun at the detective genre and the original "Milky Holmes" series. The tone is consistently light and whimsical, with a focus on character interactions and slapstick comedy rather than intricate plotlines.

Supporting characters include the members of the Milky Holmes team—Sherlock Shellingford, Nero Yuzurizaki, Elly Himeyuri, and Cordelia Glauca—who occasionally appear to provide guidance or contrast to Alice and Sherlock's antics. The series also features recurring antagonists, such as the Phantom Thief Empire, who add an element of rivalry and conflict, though their schemes are often as comically inept as the protagonists' detective work.

Overall, "Futari wa Milky Holmes" is a comedic take on the detective genre, focusing on the misadventures of two aspiring detectives and their humorous attempts to emulate their idols. The series prioritizes humor and character-driven storytelling, offering a lighthearted and entertaining experience for viewers familiar with the "Milky Holmes" universe.