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Background: In recent years, there have been great improvements in the therapy of renal cell carcinoma. Nevertheless, the therapeutic effect varies significantly from person to person. To discern the effective treatment for different populations, predictive molecular biomarkers in response to target, immunological, and combined therapies are widely studied. Conclusion: This review summarized those studies from three perspectives (SNPs, mutation, and expression level) and listed the relationship between biomarkers and therapeutic effect, highlighting the great potential of predictive molecular biomarkers in metastatic RCC therapy. However, due to a series of reasons, most of these findings require further validation. [ABSTRACT FROM AUTHOR]