The show runs as narrative, single-narrator investigative journalism rather than studio interviews or panel discussion, with reporters travelling to the places where cases happened and interviewing family members, police, and witnesses on tape. Its own episodes trace the aftermath of the Cleo Semaganis Nicotine case, including a 2025 episode on Letitia Racine, an Indigenous child caught in a custody dispute that produced the precedent-setting Racine v. Woods Supreme Court ruling. A large share of the sampled feed, however, consists of 'introducing' episodes that preview other CBC true crime series, effectively using Missing & Murdered as a cross-promotional entry point into CBC's investigative podcast network. David Ridgen, host of Someone Knows Something, appears repeatedly reporting on cold cases like the 1993 disappearance of Christine Herron and the 2021 disappearance of Jacqueline Furlan-Smith in Costa Rica. Adrian Stimson, an Indigenous artist from the Siksika Nation, hosts Forged, a CBC/ABC series on the Norval Morrisseau art-fraud investigation also cross-posted here. Guests tend to be family members of missing or murdered people, investigating police officers, journalists holding archival recordings, and, in the Forged case, art world figures like curator Gerald McMaster and musician Kevin Hearn. Cases frequently involve police missteps, such as an early assumption that a missing teenager was a runaway, or interrogation tactics used on suspects who were later cleared. The production style favors scene-setting narration and first-person witness testimony over expert panels or news-style recaps. Listeners drawn to Canadian true crime, cold-case journalism, and Indigenous justice issues are the core audience, and the feed doubles as a discovery point for other CBC true crime shows they may not otherwise encounter.