在第四季（2021年）中，故事主线的审讯组意外解散，每个人被分配到新的岗位，各自踏上不同的道路。在此背景下，第五季将延续2022年新春特别剧，审讯组终于迎来久违的期待已久的重组。以真壁有希子（天海祐希 饰）为首，管理官·梶山胜利（田中哲司 饰）、玉垣松夫（塚地武雅 饰）、菱本进（でんでん 饰）、小石川春夫（小日向文世 饰）等审讯团队将面对系列史上最强的嫌疑人。
“百晓山庄”坐落于一片毒瘴密林中，数十年来都是一处神秘禁地。在山庄百晓夜宴到来之际，庄主（姜凯文 饰）竟然神秘失踪。死囚叶礼（管栎 饰）自告奋勇，联合大理寺捕快化乾坤（杨宇斌 饰）一同探案，二人以身入局，却意外掀开了山庄背后的遮天阴谋……
As Murder, She Wrote saunters through its sixth (of an eventual 12) season, star Angela Lansbury maintains her eternally buoyant and inquisitive air as Jessica Fletcher, professional writer and amateur sleuth. Though Jessica continued to investigate murders in her home town of Cabot Cove and elsewhere (in the worlds of high finance, opera, and voodoo, among other settings), this season began the practice of guest detective episodes, introduced by Jessica as either a story she wrote or a tale told by a friend, but starring a variety of quirky investigators: An ex-football player (Ken Howard, The White Shadow) paired with a clever poodle; a television crime-show producer who solved crime in real life (Diana Canova, Soap); a stout Irish detective (longtime character actor Pat Hingle); an abrasive homicide cop (Barry Newman, Vanishing Point); as well as recurring Murder, She Wrote characters like former jewel thief Dennis Stanton (Keith Michell) and British secret agent Michael Haggerty (Len Cariou). The producers were obviously hoping to use Murder, She Wrote's popularity to spin-off new series, but nothing from this season took off and viewer resistance soon brought the practice to an end. Executives must have been surprised to discover that, though murder mysteries are plot-driven, this show's success depends heavily on the undeniable charm of star Lansbury. Still, these one-off episodes are of a consistent quality with Lansbury's, and viewers open to variety will enjoy them just as much. The rest of the season features the usual astonishing array of guests, including movie stars old (Donald O'Connor, Singin' in the Rain) and recent (Elliott Gould, The Long Goodbye), television stalwarts (Shirley Jones, The Partridge Family; Jerry Stiller, The King of Queens; Doris Roberts, Everyone Loves Raymond; Kevin Tighe, Battlestar Galactica; and Gavin McLeod, The Love Boat), and D-list celebrities to die for (Dack Rambo, Morgan Brittany, Susan Anton, and more).
