Background and Objectives: Modified radical mastectomy (MRM) is a common surgical procedure, with outcomes that are influenced by the instruments used in the operation. This meta-analysis aimed to compare “cold cutting” or “traditional” techniques and monopolar or bipolar electrocautery. Materials and Methods: A comprehensive search of five databases was conducted, with only studies of adult patients undergoing MRM in clearly defined groups selected. Data from 12 RCTs and 3 cohort studies summarizing 1372 participants was extracted and then synthesized using random-effects models. Risk of Bias was assessed for each of the included studies using the RoB-2 or ROBINS-I tool. Results: Scalpel or scissor use in dissection and flap raising was associated with a significantly lower risk of seroma formation (LogOR = −0.90, 95% CI: −1.26 to −0.54, p < 0.01). Conversely, electrocautery demonstrated advantages including reduced operative time (MD = −13.14 min, 95% CI: −19.58 to −6.70, p < 0.01) and decreased intraoperative blood loss (MD = −171.60 mL, 95% CI: −259.35 to −84.41, p < 0.01). No statistically significant differences were observed in total drain output (MD = −16.45 mL, 95% CI: −170.96 to 138.06, p = 0.83) or duration of drainage (MD = 0.41 days, 95% CI: −0.41 to 1.23, p = 0.32). Similarly, rates of infection, ecchymosis, and flap necrosis did not differ significantly between techniques. Conclusions: Electrocautery should be employed in patients who benefit from a shorter operative time and lower blood loss, while patients in better clinical condition should benefit from cold cutting techniques. Data on patient-reported outcomes and wound cytokine levels were sparse and inconsistent. This meta-analysis was registered in PROSPERO (ID: CRD420251059886).