The management of advanced genitourinary tumors is rapidly evolving thanks to the clinical availability of several targeted drugs with different mechanisms of action. Among clinicians, in-depth knowledge of all the aspects of the disease, together with the capacity to interpret and accurately correlate clinical data and imaging findings, are strongly needed. Moreover, the optimization of treatment sequences might lead to better disease control with respect to prognostic categories, radiological monitoring and newer biomarkers. Among the genitourinary tumors, only few data are available on bladder, testicular and penile cancers. Our report is supported by scientific and clinical experience in renal cell carcinoma and prostate cancer.