Bladder cancer is a widespread and highly heterogeneous malignancy. Moreover, bladder cancer recurrence and treatment failure are common, making this disease a challenge for genito-urinary surgeons. Precision medicine represents a new medical concept and model. It is based on personalized medicine, and employs genomics, proteomics, and other omics and cutting-edge medical technologies to classify disease at the molecular level, enabling accurate identification of its cause and therapeutic targets, ultimately offering precise, personalized medicine. The existence of heterogeneity in bladder cancer, resulting in different molecular phenotypes, constitutes a huge challenge for precision medicine. Studying phenotypic differences will be of substantial clinical significance and far-reaching research value with respect to the natural history of tumor development, reduction of drug resistance, the early diagnosis and prognosis of patients with bladder cancer, and the realization of fully developed precision medicine. This paper reviews the possible mechanisms underlying tumor heterogeneity and their impact on precision medicine. The manner in which precision medicine may be performed in the presence of bladder cancer heterogeneity and the prospects of this discipline are also discussed.