Herein, we report the successful management of a 63-year-old woman with comorbid major depressive disorder (MDD) and fibromyalgia syndrome (FMS). The patient exhibited a 3-year history of generalized pain, fatigue, poor sleep, and depression. Initially diagnosed with MDD, persistent symptoms led to an additional diagnosis of FMS. The treatment involved a multidisciplinary approach involving pharmacological interventions (venlafaxine, pregabalin, and lorazepam) and non-pharmacological strategies (psychotherapy and electroacupuncture). Significant improvement was observed in depressive and pain symptoms. By day 15, the patient exhibited marked improvement in Hamilton Depression Rating Scale-24 (40 – 14), Hamilton Anxiety Rating Scale (27 – 11), and Visual Analog Scale pain scores (8 – 0). The 3-month follow-up revealed sustained improvement, and the patient resumed normal daily activities. This case emphasizes the importance of thorough evaluation, consideration of comorbid conditions, and the effectiveness of a multidisciplinary approach in managing complex cases of comorbid MDD and FMS. Furthermore, personalized treatment strategies are required to achieve optimal long-term outcomes.