Urothelial cancer (UC) represents one of the most frequent malignancies, which causes about 150,000 deaths per year worldwide. To date, only a few chemotherapeutic drugs have been approved against UC, showing poor results, and limited effective molecular markers. In the last years, several studies have evaluated the correlation between bladder cancer and phlogosis, showing that some cytokines produced by different stimuli can enhance invasion and migration of tumor cells. In more recent years, antibodies blocking immune checkpoints have exhibited oncologic efficacy, including increased overall survival, in various tumor types. To date, several studies evaluated the role of immune-checkpoint inhibitors in metastatic UC showing exiting results, compared to those of classic chemotherapeutic regimens. In this review, we summarized data on inflammatory mediators and discussed implications for treatment with new immune-related drugs in UC patients.