Introduction: Celiac plexus neurolysis (CPN) has been developed as adjunctive therapy to medical management (MM) of abdominal pain associated with unresectable pancreatic cancer. We aimed to conduct a systematic review and meta‐analysis to obtain updated and more accurate evidence on the efficacy of additional types of CPN, including endoscopic ultrasound‐guided CPN (EUS‐CPN). Methods: On March 16, 2021, we performed searches of PubMed, Web of Science, and CENTRAL for original randomized controlled trials (RCTs). We defined the primary outcome as a standardized pain intensity score with a range of 0–10, and evaluated the mean difference between the CPN + MM and MM groups at 4, 8, and 12 weeks after the initiation of treatment. We used a random‐effects model to synthesize the mean differences across RCTs. Results: We selected 10 RCTs involving 646 individuals. The synthesized mean difference in the pain intensity score between the CPN + MM and MM groups was −0.58 (95% confidence interval [CI]: −1.09 to −0.07) (p = 0.034) in favor of CPN + MM at 4 weeks, −0.46 (95%CI: −1.00 to 0.08) (p = 0.081) at 8 weeks, and − 1.35 (95%CI: −3.61 to 0.92) (p = 0.17) at 12 weeks. Conclusions: This updated meta‐analysis of CPN demonstrates its efficacy for managing abdominal pain at 4 weeks. Although there are various limitations, when abdominal pain in patients with unresectable pancreatic cancer is poorly controlled with MM alone, CPN should be an option even if the duration of effect is short‐lived, taking into account the absence of serious adverse events. [ABSTRACT FROM AUTHOR]