This comprehensive learning activity equips perioperative and ambulatory surgery nurses with essential knowledge for preventing, recognizing, and managing malignant hyperthermia (MH), a rare but life-threatening pharmacogenetic emergency triggered by volatile anesthetics and succinylcholine in genetically susceptible patients. The content covers MH pathophysiology including RYR1 genetic mutations and calcium dysregulation, evidence-based preoperative screening protocols to identify at-risk patients, prevention strategies using trigger-free anesthesia techniques, early crisis recognition through ETCO₂ monitoring and vital sign assessment, and step-by-step emergency management following MHAUS guidelines including immediate dantrolene administration at 2.5 mg/kg with repeated dosing until symptom resolution. Emphasis is placed on the critical importance of rapid response within the first minutes of trigger exposure, maintaining adequate dantrolene supplies, simulation-based competency training, and post-crisis monitoring for recrudescence, providing nurses with actionable protocols to ensure optimal patient outcomes in this time-sensitive emergency.