Aim: To perform a systematic review to determine the efficacy/safety of PGx-guided opioid therapy for chronic/postoperative pain. Materials & methods: We searched PubMed and other specialized databases. Articles were considered if they compared the efficacy/safety of PGx-guided opioid therapy versus usual care. The risk of bias assessment was performed using Cochrane tools. Results: A total of 3794 records were retrieved. Only five were included for data extraction. A lower requirement of analgesics during postoperative in the PGx-guided intervention arm was reported in two studies. Also, two studies reported significant pain improvement in favor of the PGx-guided therapy when analyzing the subgroup of patients with a high-risk CYP2D6 phenotype. Conclusion: Despite the findings described, information on the efficacy/safety of this intervention is scarce.