Abstract: Immunotherapy, as an emerging oncological intervention method, has achieved significant therapeutic effects by modulating the patient's own immune system, thereby holding substantial promise for cancer treatment. However, not all patients derive significant benefits from immunotherapy. Some may experience adverse reactions, which potentially exacerbate their cancer condition. Hence, identifying biomarkers capable of predicting or monitoring immunotherapy efficacy is crucial. Metabolomics focuses on studying lowmolecular-weight metabolites within organisms. By analyzing metabolite changes under various physiological and pathological conditions, metabolomics may reveal the associations between metabolites, diseases, and their clinical treatments, thus with broad prospect of application in identifying small-molecule biomarkers for predicting immunotherapeutic efficacy. Currently, metabolomics is widely applied in cancer research, with several studies identifying metabolites associated with immunotherapy efficacy. This review summarizes recent findings in the impact of biomolecules such as sugars, lipids, and amino acids on immunotherapy efficacy, further validating the immense potential of metabolomics in identifying predictive small-molecule biomarkers for immunotherapy efficacy.