Abstract: In this review, we discussed genetic and immunological changes of bladder cancer along with relapse of this disease; however, it should be noted that in most cases, multiple genetic and immunological changes occur simultaneously or mutually dependent on each other. Many genetic mutations disrupt the function of genes involved in regulation, and conversely, chromosomal aberrations lead to changes in transcription. Pathogenesis and transition of normal urothelium of bladder into cancer are multifactorial processes. Chronic inflammation causes the initiation and progression of the main pathophysiology of invasive and metastatic cancer. A dichotomy is observed in the role of immune cells in bladder cancer. Although the immune response protects the bladder by suppressing tumor growth, certain immune cells including neutrophils, macrophages, and T-lymphocytes contribute the development and progression of the tumor.