Metabolomics, a cutting-edge omics technique, is a rapidly advancing field in biomedical research, concentrating on the elucidation of pathogenetic mechanisms and the discovery of novel metabolite signatures predictive of disease risk, aiding in earlier disease detection, prognosis and prediction of treatment response. The capacity of this omics approach to simultaneously quantify thousands of metabolites, i.e. small molecules less than 1500 Da in samples, positions it as a promising tool for research and clinical applications in personalized medicine. Clinical metabolomics studies have proven valuable in understanding cardiometabolic disorders, potentially uncovering diagnostic biomarkers predictive of disease risk. Liquid chromatography-mass spectrometry is the predominant analytical method used in metabolomics, particularly untargeted. Metabolomics combined with extensive genomic data, proteomics, clinical chemistry data, imaging, health records, and other pertinent health-related data may yield significant advances beneficial for both public health initiatives, clinical applications and precision medicine, particularly in rare disorders and multimorbidity. This special issue has gathered original research articles in topics related to clinical metabolomics as well as research articles, reviews, perspectives and highlights in the broader field of translational and clinical metabolic research. Additional research is necessary to identify which metabolites consistently enhance clinical risk prediction across various populations and are causally linked to disease progression.