Background: Endurance athletes require tailored nutrition strategies to optimize performance, recovery, and training adaptations. While traditional sports nutrition guidelines provide a foundational framework, individual variability in metabolic responses underscores the need for precision nutrition, informed by genetic, biological, and environmental factors. This scoping review evaluates the application of systems biology-driven sports nutrition for endurance athletes, focusing on ‘omics’ and wearable technologies. Methods: A scoping review of the literature was conducted in PubMed, Scopus, and Web of Science in accordance with the PRISMA-ScR checklist. Research questions, search strategies, and eligibility criteria were guided by the Population–Concept–Context framework with the following inclusion criteria: original research in English, involving endurance athletes, systems biology approaches, and nutritional interventions or continuous glucose monitoring (CGM). Results: Fifty-two studies were included, with distance runners as the most studied cohort. Eleven studies used metagenomics, eleven CGM, ten nutrigenetics, ten metabolomics, seven multi-omics, one proteomics, one epigenomics, and one lipidomics. Over half (n = 31; 60%) were randomized controlled trials (RCTs) with generally high methodological quality. Conclusions: Most studies were proof-of-concept investigations aimed at assessing biomarkers; however, the evidence linking these biomarkers to performance, recovery, and long-term health outcomes in endurance athletes remains insufficient. Future research should focus on well-powered replicated crossover RCTs, multivariate N-of-1 clinical trials, 360-degree systems-wide approaches, and the validation of genetic impacts on nutritional interventions to refine dietary guidelines.
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