Bladder cancer is the fifth most common malignancy worldwide and presents a significant diagnostic challenge due to its high recurrence rate and reliance on invasive detection methods such as cystoscopy. Current diagnostic tools, including cytology, have limited sensitivity. This study aims to identify urinary protein biomarkers that can serve as a non-invasive diagnostic tool for high-risk bladder cancer. We utilized mass spectrometry-based proteomic analysis to evaluate urinary samples from bladder cancer patients and control individuals. A combination of four protein biomarkers—Complement Factor H (CFH), Fibrinogen β (FGB), Alpha-2-macroglobulin (A2M), and Alpha-amylase pancréatique (AMY2A)—was identified as a promising diagnostic panel. These biomarkers demonstrated 100% sensitivity for detecting high-grade tumors, with a false-positive rate of 70-80%, depending on patient history. Comparative analysis with traditional cytology revealed superior sensitivity and potential for early-stage detection. These findings highlight the feasibility of a urinary proteomic approach in bladder cancer diagnosis using a combination of protein biomarkers, and provide a foundation for the development of a clinically viable, cost-effective, and less invasive screening method.