Purpose of Review <p>Treatment-emergent neuroendocrine prostate cancer (NEPC) is aggressive and lethal. As androgen receptor signaling inhibitors (ARSIs) are increasingly used in earlier disease settings, treatment-emergent NEPC becomes more prevalent, and effective therapies are urgently needed. The purpose of this review was to summarize recent progress on emerging therapeutic targets of NEPC.</p> Recent Findings <p>A multitude of therapeutic targets have emerged in NEPC over recent years. These targets may represent drivers of treatment-emergent lineage plasticity or simply be overexpressed on the surface of NEPC cells. Multiple modalities have been employed to drug these targets, with promising preclinical and clinical results.</p> Summary <p>Treatment-emergent NEPC represents a distinct and clinically significant subset of castration-resistant prostate cancer (CRPC). Emerging therapeutic approaches have demonstrated encouraging efficacy and safety profiles, offering the potential to improve patient outcomes.</p>