Abstract: The present disclosure relates generally to, inter alia, therapeutic and diagnostic methods and compositions for treatment of bladder cancer. In particular, the disclosure relates to defining pre-treatment gene signatures that are predictive of response to anti-PD-L1 therapy and to the use of such gene signatures as biomarkers to identify individuals having or suspected of having bladder cancer who are most likely to respond to an anti-PD-L1 therapy. In some embodiments, various methods for the treatment of bladder cancer in individuals identified by the diagnostic methods disclosed herein are also provided.