Significant advances in prostate cancer (PCa) treatment have occurred through the integration of molecular biomarkers and imaging with targeted therapies. While androgen receptor pathway inhibition (ARPI) remains the cornerstone of PCa therapy, the current therapeutic landscape has expanded to include a broader range of targeted agents, alongside emerging approaches that leverage disease-specific vulnerabilities. Molecular profiling has enabled the exploration of diverse therapeutic modalities, including epigenetic regulators, immune-modulating agents, metabolic pathways, kinases, and cell surface proteins. Despite this progress, further research is needed to address tumour heterogeneity and treatment-resistant phenotypes. As ARPI use moves earlier in the disease course and novel agents are incorporated into standard care, prolonging disease control may also reshape emergent resistant phenotypes and disease progression trajectories. This evolving context underscores the need to revisit agents that may now show efficacy in new therapeutic settings or when paired with complementary strategies. Here, we review the current treatment framework in PCa and highlight novel approaches and targets poised to transform clinical care.