Nutrition therapy is a complex intervention with several underlying considerations that may influence effectiveness. Considerations include the mechanism of action of the intervention and the patient phenotype, including sex, ethnicity, body composition, and the patients’ nutritional and inflammatory status. Energy and protein targets are elements of nutrition therapy that may be particularly influenced by individual patient factors. Biomarkers may provide a useful tool to monitor and individualize nutrition therapy in the future. The considerations mentioned, with many yet to be studied, highlight the rationale for more individualized interventions moving away from a ‘one-size-fits-all’ approach.