Multiple organ dysfunction syndrome (MODS) represents the progressive failure of two or more organ systems in acutely ill patients, most commonly triggered by sepsis, severe trauma, or major surgery. The pathophysiology involves a dysregulated systemic inflammatory response that causes widespread endothelial dysfunction, microcirculatory failure, and mitochondrial dysfunction across multiple organ systems simultaneously. The initial insult (infection, tissue injury) activates innate immune cells, releasing damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) that perpetuate inflammation through positive feedback loops. This creates a 'second hit' phenomenon where impaired microcirculation, oxygen utilization failure, and immune dysregulation compound the initial injury. Organ failure is quantified using the Sequential Organ Failure Assessment (SOFA) score across six systems: respiratory (PaO2/FiO2 ratio), coagulation (platelet count), hepatic (bilirubin), cardiovascular (MAP and vasopressor requirement), neurological (GCS), and renal (creatinine and urine output). Mortality increases by approximately 15-20% for each additional organ system that fails. The nurse monitors SOFA scores serially, provides organ-system-specific supportive care, administers prescribed vasoactive agents, manages mechanical ventilation with lung-protective strategies, monitors fluid balance, recognizes clinical deterioration trajectories, and communicates prognosis clearly for goals-of-care discussions.