The implementation of innovative methods of drug therapy and biotherapy into clinical practice has significantly changed the treatment tactics for metastatic urothelial cancer. Currently, treatment regimens are successfully supplemented with immunotherapy (immune checkpoint inhibitors) or targeted therapy, and the effectiveness of such combinations can be quite high, but the optimal sequence of different types of drug therapy remains to be established. The development of correct algorithms using reliable biomarkers is necessary to select the correct sequence of prescribing drugs. Until now, the expression of programmed cell death-ligand 1 (PD-L1) and changes in fibroblast growth factor receptors 1–4 (FGFR1–4) have been the fundamental markers for choosing alternative treatment regimens for metastatic urothelial cancer. At the same time, the list of useful and sufficiently informative biomarkers is expanding, and therefore we tried to summarize the available data on the known biological markers for selection of treatment tactics for metastatic urothelial cancer. © 2023 ABC-press Publishing House. All rights reserved.