Dermatophytosis is a common superficial fungal infection caused by dermatophytes. In recent years, antifungal resistance among dermatophytes has emerged as a growing clinical concern. We report the first documented case of terbinafine-resistant Trichophyton rubrum in Tunisia, occurring in a 50-year-old immunocompromised woman with systemic lupus erythematosus. She presented with a slightly scaly erythematous plaque in the inguinal folds, plantar hyperkeratosis on both feet, and onychodystrophy of the toenails. Despite topical terbinafine treatment, the patient experienced clinical progression. Antifungal susceptibility testing performed using the EUCAST E.Def 11.0 method demonstrated high minimum inhibitory concentrations to terbinafine and itraconazole. Molecular analysis identified the F397L substitution in the squalene epoxydase enzyme. Unfortunately, the patient died of heart failure. This case highlights the emergence of antifungal resistance in dermatophytes and underscores the need for routine susceptibility testing and surveillance programs.