When mechanical ventilation is required for severe hypoxemia and acute respiratory distress syndrome, mortality ranges from 30% to 65%, with worse outcomes observed in patients with hematologic malignancy and those who have undergone stem cell transplantation. Overall, acute respiratory distress syndrome mortality has improved with the use of lung protective strategies like low tidal volume ventilation and conservative fluid management. Prone positioning, another beneficial strategy, has been shown to decrease mortality, improve gas exchange, and reduce ventilator-associated lung injury. By recruiting collapsed lung units and redistributing transpulmonary pressures, prone positioning is associated with improved hemodynamics and decreased organ dysfunction. Observational studies and retrospective case series suggest that prone positioning may improve mortality in patients specifically with cancer and ARDS but in practice may be underutilized.