VEGF-target therapies have been the first-line standard of care for metastatic ccRCC and still have a relevant role in metastatic ccRCC as a partner with anti-PD1/L1 immunotherapy in first-line treatment or in monotherapy at progression, due to the natural chemoresistance and radioresistance shown by tumoral renal cells. This evidence concerns the gene VEGFA and nonpapillary renal cell carcinoma.