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Recent advances in molecular profiling, including next-generation sequencing and bioinformatic approaches, have enabled detailed characterization of tumor biology and facilitated patient stratification based on prognostic and predictive factors associated with clinical outcomes and therapeutic response. This article summarizes key biomarkers with established clinical relevance in kidney, bladder, and prostate cancers. In bladder and prostate cancer, novel insights into tumor biology have reshaped therapeutic strategies and supported the approval of targeted therapies, thereby enhancing patient care. Selecting appropriate molecular tests-such as FGFR screening in urothelial carcinoma and BRCA1/2 testing in prostate cancer-has become critical for guiding treatment decisions.