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There is ongoing controversy regarding the tumor-protective effects of regional anesthesia in patients undergoing cancer surgery. Evidence of up-to-date systematic reviews will be presented alongside recent updates on the effects of opioids and local anesthetics.In recent years, the literature regarding the effects of regional anesthesia techniques on cancer recurrence has raised many unanswered questions. Ongoing randomized controlled trials may not be able to shed light on the controversial discussion regarding the tumor protective effects of regional anesthesia because the expected effect size and event rate in those studies may be overstated.Recent more refined animal data, provides no evidence to suggest that opioids promote cancer recurrence or facilitate the development of metastatic disease.In addition, local anesthetics have promising preclinical anticarcinogenic effects that extend beyond their voltage-gated sodium channel blocking properties and could be of therapeutic value.Cancer recurrence in patients undergoing surgery remains a global burden. Current evidence suggests that regional techniques, opioid analgesia and local anesthetics in onco-anesthesia may require a tailored individual approach due to the phenotypic and genotypic heterogeneity within and between different tumors. The authors surmise that future or ongoing randomized controlled trials regarding regional anesthesia techniques and cancer outcome may not be able to reproduce clear results, as it will be challenging to prove the efficacy of one single intervention (e.g. regional anesthesia) in an otherwise complex multifactorial perioperative oncological setting.