Omicidio per appuntamento depicts the investigation of a disappearance by Vince Dreyser (Ardisson), a private detective in Rome who is searching for a vanished friend.

Vince Dreyser (George Ardisson), an American private detective working in Rome, meets with his old friend Walter Dempsey (Hans von Borsody) in the countryside.

Dempsey was in the country to be married, and the search for his whereabouts leads Dreyser into a web of organised crime, while trying to keep an eye on the hippie daughter of a wealthy client.

[5] Guerrini's screenplay, written alongside Fernando Di Leo, was based on the novel Tempo di massacro by Franco Enna; the novel's provincial setting was moved to contemporary Rome and updated with references to then-current eurospy films, particularly Ardisson's films with Sergio Sollima.

[3] Writing for AllMovie, Robert Firsching has described the film as "stylish" and "flamboyant", finding Guerrini's direction to have been influenced by the works of fellow countryman and giallo "pioneer" Mario Bava.