When critical illness is further complicated by severe respiratory failure, such as in cases of acute respiratory distress syndrome (ARDS) requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO), patients may be at an even greater risk for nutritional deficits, immobility, and persistent metabolic stress. Although highly efficacious for cardiopulmonary failure, VV-ECMO introduces the potential for additional metabolic complexities, including altered thermoregulation, increased inflammatory burden, and, traditionally, impaired physical activity from increased lengths of intensive care unit (ICU) stays and prolonged periods of bedrest. Emerging data suggest that comprehensive metabolic and rehabilitative strategies can attenuate muscle loss, reduce ICU-acquired weakness, and improve post-discharge outcomes. This narrative review will discuss the metabolic demands faced by VV-ECMO patients and current strategies to address them. We characterize the catabolic state during VV-ECMO while highlighting the metabolic demand placed on patients. We then examine nutritional support on VV-ECMO, including the assessment of energy expenditure and its limitations, optimal calorie-protein requirements, timing and route of nutritional support, and outcomes associated with nutritional adequacy based on current evidence and guidelines. Next, we explore the potential of pharmacologic agents to possibly reduce hypermetabolism and reverse catabolism. Finally, we discuss the role of physical rehabilitation in VV-ECMO patients by focusing on physical therapy, mobilization, and strategies such as awake ECMO to facilitate activity. Throughout this review, we integrate findings from recent studies and guidelines, with the goal of providing a comprehensive narrative of how to support the metabolic needs of critically ill patients on VV-ECMO.