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Breast cancer surgery results in significant postoperative pain. Pectoral nerve blocks (PECS I and II) may lessen the use of opioids during surgery and enhance pain management. This systematic review and meta-analysis assessed the efficacy of PECS blocks compared with placebo in breast cancer surgery. The Cochrane Collaboration, PubMed, CINAHL, Google Scholar, and grey literature were all thoroughly searched. We only included randomized controlled trials (RCTs) that compared PECS I or II blocks to a placebo. Mean differences (MD) and risk ratios (RR) were calculated for primary and secondary outcomes. Meta-analysis was conducted using RevMan 5.4, and evidence was appraised using the GRADE system. Twenty-two RCTs were included. PECS blocks significantly decreased pain scores up to 48 hours after surgery during activity (MD, -1.66) and at rest (MD, -1.38). Additionally, they decreased the use of opioids during surgery (MD, -5.28) and after surgery (MD, -9.82), extended the time until first rescue analgesia (MD, 4.95 hours), and decreased PONV (RR, 0.48) with no effect on chronic pain (RR, 0.40). PECS blocks support their role in multimodal analgesia by improving postoperative pain control, lowering the need for opioids, and promoting recovery following breast cancer surgery.