Despite advances in prostate cancer screening and treatment, available therapy options, particularly in later stages of the disease, remain limited and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in significant variability in outcomes across patients. Disease classification based on genomic sequencing is a promising approach to identify patients whose tumors exhibit actionable targets and make more informed treatment decisions. Here we discuss how we can accelerate precision oncology to inform broader genomically-driven clinical decisions for men with advanced prostate cancer, drug development and ultimately contribute to new treatment paradigms.