AGPAT9, AQP7, HMGCS2, KLF15, MLXIPL, and PPARGC1A exhibited significant prognostic potential, and MLXIPL and PPARGC1A were significantly correlated with immune cell signatures for ccRCC patients, thus revealing the relevance of monitoring and manipulating the TME for ccRCC prognosis and precision immunotherapies. Here, HMGCS2 is linked to nonpapillary renal cell carcinoma.