Evolving Landscape of Precision Medicine in Bladder Cancer: From Challenges to Clinical Impact

ABSTRACT Bladder cancer (BCa) remains one of the most challenging urological malignancies to treat because of its marked molecular heterogeneity, high recurrence rates, and variable therapeutic responses. However, the emergence of precision oncology has transformed BCa research, offering unprecedented opportunities for patient‐specific interventions. In this review, we provide an updated synthesis of recent advances in the molecular characterization, diagnostic innovations, and therapeutic strategies for managing BCa. We outline the molecular landscape, emphasizing recurrent genomic alterations, such as FGFR3 , TP53 , RB1 , ERBB2 , and PIK3CA mutations, and their differential prevalence in non‐muscle‐invasive versus muscle‐invasive disease. Additionally, the refinement of BCa molecular subtyping using transcriptomic and epigenetic profiling with predictive and prognostic value has been delineated. Similarly, we discuss the role of the tumor microenvironment as a critical determinant of therapeutic response, with immune cell infiltration, stromal remodeling, and angiogenic programs guiding both prognostic assessment and treatment design. On the therapeutic front, we also emphasize the precision approaches advancing through FGFR inhibitors, HER2‐directed agents, PI3K/AKT/mTOR modulators, immune checkpoint blockade, antibody‐drug conjugates, and novel modalities, such as RNA therapeutics and oncolytic platforms. Despite these advancements, this study also narrates the various challenges in BCa, such as intratumoral heterogeneity, clonal evolution, resistance mechanisms, and genomic testing disparities. Moreover, the integration of multi‐omics, spatial transcriptomics, single‐cell technologies, artificial intelligence‐powered predictive models, and liquid biopsy‐guided monitoring can also revolutionize clinical decision‐making. Overall, precision medicine is transforming the approach to managing BCa, thus supporting the implementation of tailored and effective personalized therapies to patients.