Simple SummaryThe treatment of urothelial carcinoma is challenging. While known therapies are effective, the results can be variable. Known treatment modalities include transurethral resection of the bladder tumor, intravesicular BCG, chemotherapy, immune check point inhibitors, and antibody drug conjugates. Finding certain patient and tumor characteristics to determine responders to therapy can help personalize the treatment approach and optimize results. Precision medicine offers a solution to this problem by providing clinicians with tools such as liquid biopsies, prognostication models, and biomarkers to identify essential patient characteristics. Furthermore, precision medicine improves treatment efficacy by identifying and exploiting specific targets. In this review, we discuss available tools in precision medicine, describe ongoing clinical trials, and identify areas for future study.AbstractThe treatment of urothelial carcinoma (UC) is challenging given its molecular heterogeneity and variable response to current therapies. To address this, many tools, including tumor biomarker assessment and liquid biopsies, have been developed to predict prognosis and treatment response. Approved therapeutic modalities for UC currently include chemotherapy, immune checkpoint inhibitors, receptor tyrosine kinase inhibitors, and antibody drug conjugates. Ongoing investigations to improve the treatment of UC include the search for actionable alterations and the testing of novel therapies. An important objective in recent studies has been to increase efficacy while decreasing toxicity by taking into account unique patient and tumor-related factors—an endeavor called precision medicine. The aim of this review is to highlight advancements in the treatment of UC, describe ongoing clinical trials, and identify areas for future study in the context of precision medicine.