PSMA-PET should be used in staging high-risk prostate cancer to detect metastatic disease and better stratify patients for individualized treatment. In the era of Androgen Receptor Pathway Inhibitors (ARPIs), Androgen Deprivation Therapy (ADT) alone should be considered an undertreatment for the majority of the patients. Based on current data in the literature, the most effective therapeutic strategy seems to be the combination of intensified systemic treatment (including ADT + ARPI) and radiotherapy for the primary tumor. The role of cytoreductive radical prostatectomy is currently being investigated as well as metastasis-directed therapy to metastatic sites.