There is a marked inflammatory and hypermetabolic response following a burn injury. The interlinked responses are more pronounced than for other forms of trauma and can persist for ≥3 years post-injury in burned patients. After a burn, patients have an increased risk of diseases of ageing including cancer, diabetes and cardiovascular disease, highlighting the need for effective long-term strategies to ameliorate the stress response post-burn. Current therapeutic strategies for post-burn recovery include removal of damaged tissue with surgical excision and wound repair, nutritional supplementation and rehabilitative exercise. These strategies aim to minimize the hypermetabolic and inflammatory responses, as well as reducing the loss of lean body mass. This review briefly summarises the inflammatory and hypermetabolic responses and provides an update on the current therapeutic strategies for burned patients. The review examines the persistent nutritional challenge of ensuring sufficient energy intake of each macronutrient to fuel the hypermetabolic and counteract the catabolic response of burn injury, whilst reducing periods of hyperglycaemia and hypertriglyceridemia. Patients require individualized treatment options tailored to unique systemic responses following a burn, facilitated by a precision medicine approach to improve clinical and physiological outcomes in burned patients. Thus, this review discusses the utility of metabolic flexibility assessment to aid clinical decision making and prescription relating to nutritional supplementation and rehabilitative exercise in the burned patient.