In recent decades, serum tumor markers (STMs) have emerged as valuable adjuncts in early cancer detection and post-treatment surveillance. STMs are inexpensive, minimally invasive, and readily accessible tools that can be used to diagnose cancers, monitor patients' responses to treatment, and even detect recurrence without imposing additional burdens on patients. Emerging evidence has demonstrated the reliability of STMs in the prognostication of bladder cancer (BC). However, their potential role extends beyond prognostication. This review intends to provide a multidimensional picture of STM applications in muscle-invasive bladder cancer (MIBC). In addition, we supplement this review with real-life clinical experiences from our institution to further illustrate the clinical feasibility of STMs in MIBC.