Bladder cancer is a highly heterogeneous malignant tumor of the urinary system with high recurrence rates, posing significant challenges in its diagnosis and treatment. Advances in multi-omics research have elucidated the molecular mechanisms underlying the pathogenesis and progression of bladder cancer, including driver gene mutations (e.g., FGFR3, TP53/RB1), dysregulation of signaling pathways (such as PI3K/AKT/mTOR and RAS-MAPK), epigenetic alterations, non-coding RNA networks, tumor microenvironment remodeling, and metabolic reprogramming. This review systematically summarizes recent progress in translational research bridging molecular mechanisms to breakthroughs in precision therapy, covering the clinical applications and challenges of FGFR inhibitors, immune checkpoint inhibitors, antibody-drug conjugates, and gene therapies. Translational efforts are increasingly relying on molecular subtyping to develop subtype-specific treatment strategies. Although significant advances have been made in precision therapy for bladder cancer, critical research gaps remain, including tumor heterogeneity, therapy resistance, and insufficient validation of biomarkers. Future research directions emphasize the potential of liquid biopsy for non-invasive diagnosis and dynamic monitoring, rational combination therapies, multi-omics data integration, and artificial intelligence in advancing personalized treatment, providing a systematic and forward-looking perspective on precision medicine in bladder cancer.

Bacillus Calmette–Guérin (BCG) immunotherapy has been a cornerstone treatment for non-muscle-invasive bladder cancer for decades and still faces challenges, such as severe immune adverse reactions, which reduce its use as a first-line treatment. This review examines BCG therapy’s history, mechanisms, and current status, highlighting how nanotechnology and bioengineering are revitalizing its application. We discuss novel nanocarrier systems aimed at enhancing BCG’s efficacy while mitigating specific side effects. These approaches promise improved tumor targeting, better drug loading, and an enhanced stimulation of anti-tumor immune responses. Key strategies involve using materials such as liposomes, polymers, and magnetic particles to encapsulate BCG or functional BCG cell wall components. Additionally, co-delivering BCG with chemotherapeutics enhances drug targeting and tumor-killing effects while reducing drug toxicity, with some studies even achieving synergistic effects. While most studies remain experimental, this research direction offers hope for overcoming BCG’s limitations and advancing bladder cancer immunotherapy. Further elucidation of BCG’s mechanisms and rigorous safety evaluations of new delivery systems will be crucial for translating these innovations into clinical practice.