Background <p>Robot-assisted prostatectomy (RAP) can cause significant post-operative pain. Opioids are commonly used for relief, but they pose risks such as side effects and potential dependence. To reduce opioid usage, regional anesthesia approaches, especially various nerve block techniques, have been developed. However, evidence comparing the effectiveness of these different nerve blocks remains limited.</p> Methods <p>A systematic review was conducted to evaluate the effectiveness of different nerve block techniques on post-operative pain control after RAP. Databases were searched for randomized controlled trials (RCTs) that compared nerve blocks with either standard care or other regional anesthesia techniques. The primary outcomes assessed were pain scores, opioid consumption, recovery metrics, and treatment-related adverse effects.</p> Results <p>Eight studies comprising 696 participants were included. Intrathecal morphine consistently demonstrated the most significant reduction in post-operative pain and opioid use, though with increased incidence of pruritus and other side effects. Erector spinae plane blocks (ESPB) and rectus sheath blocks (RSB) were also effective, offering a favorable balance of analgesia and safety. Quadratus lumborum blocks (QLB) and pudendal nerve blocks (PNB) were found to effectively reduce pain, opioid usage, and side effects when they were used in a multimodal analgesic protocol. Alternatively, transversus abdominis plane blocks (TAPB) and caudal blocks were found to have mixed or no opioid-sparing effects. Because of methodological heterogeneity between studies, direct comparisons between blocks were limited.</p> Conclusion <p>Regional anesthesia techniques improve post-operative pain control and reduce opioid use after RAP. Given the lack of definitive superiority among techniques, analgesia should be individualized and incorporated into multimodal, opioid-sparing protocols. More large-scale, head-to-head trials are needed to guide optimal nerve block selection.</p>