Forty randomized controlled trials including patients undergoing total knee arthroplasty (TKA) were included in this systematic review and meta-analysis comparing various intraoperative anesthetic therapies. Pooled outcomes of interest included pain relief measured by the visual analog scale (VAS) or area under the curve (AUC) and morphine consumption in morphine equivalents, postoperatively. Local infiltration anesthesia (LIA) with saphenous nerve block (SNB) showed the best pain relief on postoperative days (PODs) 1 and 2 and the most significant reduction in morphine consumption on PODs 1 and 3. Femoral nerve block (FNB) provided the largest effect on pain relief on POD 3, and liposomal bupivacaine (LB) showed the most significant reduction in morphine consumption on POD 2. LIA with SNB offers superior analgesic effects and lower morphine consumption, making it a preferred choice for improving postoperative outcomes in TKA patients.