Randomised controlled trials are the ‘gold standard’ approach in nutrition research to show a causal relationship between a dietary intervention and clinically relevant outcomes at the population level. Here we review why different study designs are needed to establish the efficacy of dietary interventions at the individual level and to better account for relevant factors that can also influence the outcomes. Over the past decade, precision nutrition approaches have been developed as a new way to measure the effectiveness of dietary interventions at the individual and population level. Precision nutrition aims to determine the individual factors that are associated with differences in responses to dietary interventions. This is complex, typically needing studies with a large number of participants and using advanced statistical approaches and machine-learning algorithms to identify predictors that can explain why individuals do or do not respond to consuming specific foods, meals or diets, for a given outcome. N-of-1 study designs, which are new to nutrition science, offer a robust alternative approach to assess how an intervention and everyday behaviours affect individual health outcomes. They utilise repeated measures within individuals, rather than baseline and end measures in a larger number of participants, to provide the statistical power required to determine an individual’s responsiveness to an intervention. The adoption of new study designs and modelling approaches, particularly the N-of-1 approach, to examine responses to interventions within individuals, will help to further the understanding of the relationships between diet and health within individuals more effectively and accurately.