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Abstract. Bladder cancer is a complex disease of the urinary system with high morbidity and mortality. Recently, the introduction of immunotherapies such as immune checkpoint inhibitors (eg, programmed cell death protein 1/programmed death-ligand 1) has proven to be a reliable means of improving survival outcomes, including patients with limited response to conventional treatment. Nevertheless, difficult questions remain in clinical practice, such as how to select appropriate patients for personalized treatment, how to predict and assess therapeutic efficacy in advance, and how to enhance the therapeutic benefits of immunotherapy treatment. These issues require urgent attention. Herein, we describe recent clinical applications of immune checkpoint inhibitors in bladder cancer therapy, examine underlying mechanisms for treatment failure in a subset of patients, and discuss potential approaches to improve their therapeutic effects.