The advent of immunotherapy has enriched the therapeutic landscape of UC by challenging the existing therapeutic limitations of the chemotherapy era. Despite improved survival outcomes with immunotherapeutic agents, only 30% of patients who qualify for treatment experience lasting clinical benefit, possibly reflecting heterogeneous disease biology. In order to understand the best treatment decisions and to guide recommendations, we aimed to systematically evaluate the available evidence in the literature regarding the safety and efficacy of immunotherapy agents in patients with advanced uroepithelial cancer.