Being among the five most common malignancies worldwide, bladder cancer is a major cause of morbidity and mortality, and a great burden to healthcare systems. Due to a high disease recurrence rate, patients are under continued surveillance for early detection of new tumor developments and face undergoing multiple invasive procedures. Consequently, The development of accurate assays that can detect and monitor bladder cancer non-invasively through urinalysis would be a major advance, benefiting both patients and healthcare systems. Through our proteomics and genomics programs, we have identified a diagnostic molecular signature that can be applied to detect bladder cancer in voided urine samples. Through multiple validation studies, technological developments, and engagement with the FDA, we are now poised to begin clinical trials to refine and establish a clinical laboratory test that can guide clinical management of patients at risk for bladder cancer.