The anthological film series as a part of the Universal Horror label[failed verification], stars Lon Chaney Jr. in a number of similar roles, with plots that do not overlap though they are thematically related.

[2][better source needed] The film series originated from the Golden Age radio dramas titled Inner Sanctum and created by Himan Brown; which were in turn based on the Simon & Schuster imprint of the same name.

[3] Though the novels are generally associated with mysteries, the imprint was additionally used for drama and romance; with each genre being published in green, blue, and red colored book covers, respectively.

[6] Initially, Pivar was hired to produce two Inner Sanctum Mystery films each year, with each installment starring Lon Chaney, Jr. and Gale Sondergaard.

[1] Edward Dein suggested that at Chaney Jr.'s request, the scripts incorporated lines for an audible inner "stream of consciousness" voiceovers that the audience would hear.

[7] When Dr. Mark Steele finds himself unable to recollect the last several days of his life, he's further disturbed to learn that his wife Maria has been found brutally murdered.

Disturbed by the situation and hoping to recover his repressed memories, he requests that his nurse Stella perform hypnosis to determine whether he is a scheming murderer.

Though the medical examination determines that it was caused by a heart attack, Alex is overcome with guilt and retires from his stage show believing that the incident was his fault.

[12] Wayne Fletcher, a successful attorney engages in an affair with his secretary Donna Kincaid, while the pair plan to be married once he divorces his wife.

[21] Kim Newman reviewed the series in Sight & Sound in 2021, describing it as "straddling whodunnit and horror" and that "the films vary in quality but mostly deliver as strange entertainment.