My Favorite Murder is co-hosted by Karen Kilgariff and Georgia Hardstark, who alternate telling true crime stories to each other in a friend-to-friend, conversational style rather than a polished investigative format. The core numbered episodes center on one host narrating a case while the other reacts and riffs, drawing on serial killers, cold cases, and lesser-known poisoners and bombers, including Caroline Grills and Jack Gilbert Graham. A recurring minisode format features listener-submitted stories, often framed as 'hometown murders' or close-call encounters like risky first dates and accidental 911 calls. 'Rewind' episodes revisit older or live tour recordings, such as shows taped at the Enmore Theatre in Sydney and the Boulder Theater in Colorado, with the hosts adding present-day commentary on the tour, audience interactions, and hecklers. Less frequently, solo episodes depart from true crime entirely to cover women's history, as in an episode on mountaineer Junko Tabei. Producer Steven Ray Morris is a recurring off-mic presence referenced in running jokes across episodes. The show sits within the Exactly Right podcast network, and episodes frequently carry promotional segments for sibling shows like Wicked Words and Dear Chelsea. The audience is largely the show's self-identified 'Murderino' fan community, and episodes sometimes touch on fan-culture topics such as live-show etiquette and the hosts' own discussion of true-crime 'fatigue.' Tone stays comedic and casual even when the underlying material is violent, with the hosts periodically addressing the ethics of treating real murders as entertainment. Overall it functions as a long-running, community-driven true crime comedy franchise built on the hosts' friendship and live touring history rather than formal reporting.