The treatment of advanced prostate cancer (PCa) primarily based on androgen deprivation therapy (ADT); however, patients inevitably progress to the castration-resistant prostate cancer (CRPC) stage. Despite the recent advancements in CRPC treatment with novel endocrine drugs that further inhibit androgen receptor signaling, resistance ultimately develops, underscoring the urgent need for new effective therapeutic strategies. Therapeutic cancer vaccines, a form of immunotherapy, exert anti-cancer effects by activating the host's immune system. Over the past few decades, various conventional therapeutic PCa vaccines based on cells, microbes, proteins, peptides, or DNA have been developed and tested in patients with advanced PCa. These attempts have largely failed to improve survival, with the sole exception of sipuleucel-T, which extended the median overall survival of asymptomatic or minimally symptomatic metastatic CRPC (mCRPC) patients by four months. The rapid development and high efficacy of mRNA vaccines during the COVID-19 pandemic have garnered worldwide attention. Compared to conventional vaccines, mRNA vaccines offer several unique advantages, including high production efficiency, low cost, high safety, strong immune response induction, and high adaptability and precision. These attributes make mRNA vaccines a promising frontier in the treatment of advanced PCa.Copyright © 2025. Published by Elsevier B.V.