Background: Neuroleptic Malignant Syndrome (NMS) is a rare but life-threatening potentially fatal adverse condition most commonly associated with dopamine receptor antagonists. It is characterized by hyperthermia, generalized muscular rigidity, autonomic dysregulation, and elevated serum creatine kinase levels. Prompt recognition and intervention are critical for reducing morbidity and mortality. Case Report: A 61-year-old female with multiple comorbidities developed atypical NMS following abrupt discontinuation of long-acting depot antipsychotic therapy. The patient presented with fever, altered mental status, autonomic dysfunction, and progressive respiratory failure without marked rigidity or significant elevation in creatine kinase levels. Her condition was further complicated by sepsis and hemodynamic instability, necessitating admission to the intensive care unit (ICU) and mechanical ventilation. The diagnosis was established based on the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders and clinical judgment. The patient responded favorably to bromocriptine and other supportive interventions. Conclusion This case highlights the diagnostic complexity of atypical NMS, particularly in elderly patients undergoing depot antipsychotic therapy. A high index of clinical suspicion and prompt multidisciplinary intervention are essential to improve outcomes in such challenging presentations.