In this review, we report the physiologic role of IL-8, its involvement in the process of carcinogenesis, its initial assessment as a clinical biomarker in cancer, and how these recent analyses of IL-8 in clinical trials may pave the way for a more thorough investigation of IL-8 as a prognostic and predictive biomarker of response to ICI and/or TKI therapy in mRCC. The gene discussed is CXCL8; the disease is cancer.