Patients with castration-resistant prostate cancer (CRPC) who received a novel androgen receptor pathway inhibitor (ARPI) often show drug resistance in response to treatment. Tumors acquire androgen receptor (AR)-independent subtypes, so that cancer cells no longer depend on AR pathway to continue to grow. More and more studies have shown that after CRPC patients received ARPI treatment, some patients not only failed to achieve the clinical benefit but also experienced the evolution of tumor progression, that is, neuroendocrine prostate cancer (NEPC). NEPC is closely related to poor prognosis. So far, rare effective and reliable drugs have been found clinically to treat NEPC. This article aims to summarize the mechanism of NEPC and the molecular targets, and provide references for the diagnosis and treatment of NEPC patients.