Bladder cancer belongs to the high mutation burden cancers due to the genetic alterations in non-conventional DNA repair systems such as ERCC2. Bladder cancer is characterized by mutations of FGFR3, HER-2 and HRAS and translocations of FGFR3 and PPARG. The papillary luminal form is the FGFR3 mutant, the unstable luminal version is the HER-2 mutant, while in the basal form EGFR amplification can be detected. Prognosis of bladder cancer is also defined by molecular features such as the claudin and MMP expressions and chromosomal alterations detected by UroVysion test. Last but not least, molecular aberrations are strong predictive factors: high mutation burden defines sensitivity toward immunotherapies, ERCC2 and HER-2 mutations define sensitivity toward chemotherapy, BRCA1/2 mutations define sensitivity to PARP inhibitors, tumors with FGFR3 mutation are prone to FGFR inhibitors while HRAS mutations define sensitivity to farnesyltransferase inhibitors.