Current prostate cancer (PCa) treatment options include hormonal therapy, chemotherapy, immunotherapy, and radiotherapy; however, a lack of targeting and overall efficiency has failed to improve survival rates or reduce unwanted side‐effects in advanced stage PCa patients. The modification of existing therapeutics, including their reformulation as nanomedicines, can increase stability in plasma, enhance tumor targeting, and improve pharmacokinetics to foster improvements in patient outcomes. This review now describes those nanomedicinal approaches to advanced PCa treatment under evaluation in both preclinical and clinical studies. Despite the current advantages provided by nanomedicine in PCa treatment, there exists the opportunity to improve the design of novel therapeutic approaches. Therefore, this review also highlights the importance of identifying novel functional biomarkers to stratify patients and guide nanomedicinal design. Finally, the authors describe strategies employed to enhance the passive accumulation of nanomedicines in tumors and discuss the enormous potential of combination therapies that target tumor cells and the all‐important tumor microenvironment to reduce tumor growth and overcome therapeutic resistance.