Early detection of urothelial cancer offers the potential for effective and successful treatment. Despite previous efforts, currently, there is not a well-validated, recommended screening program in any country. This integrative, literature-based review provides details on how recent molecular advances may further advance early tumor detection. The minimally invasive liquid biopsy is capable of identifying tumor material in human fluid samples from asymptomatic individuals. Circulating tumor biomarkers (cfDNA, exosomes, etc.) are very promising and are attracting the interest of numerous studies for the diagnosis of early-stage cancer. However, this approach definitely needs to be refined before clinical implementation. Nevertheless, despite the variety of current obstacles that require further research, the prospect of identifying urothelial carcinoma by a single urine or blood test seems truly intriguing.