Background: Anaesthetic choice, regional anaesthesia (RA), general anaesthesia (GA), or their combination, influence surgical stress responses, perioperative recovery, and patient satisfaction. Understanding their comparative effects is important for optimising Enhanced Recovery after Surgery (ERAS) strategies. We aimed to systematically review evidence comparing RA, GA, and combined anaesthesia in terms of recovery outcomes, opioid use, patient satisfaction, perioperative complications, and molecular stress responses. Methods: A PRISMA-guided systematic review was conducted across PubMed/MEDLINE, Embase, Scopus, and Cochrane databases (2010–2025). Eligible studies included adult surgical patients receiving RA, GA, or both, with direct comparison of perioperative outcomes. Randomised controlled trials and prospective observational studies were considered. Outcomes included recovery quality, pain control, opioid consumption, perioperative complications, mortality, and molecular/biological markers. Results: Seven studies met the inclusion criteria (n=30–322 per study), spanning hand, breast, maxillofacial, orthopaedic, and hip fracture surgeries. RA—alone or with sedation/GA—was frequently associated with similar or improved recovery quality, reduced perioperative opioid use, and in some cases, attenuated molecular stress responses compared with GA. Functional recovery and satisfaction outcomes were generally comparable. Mortality and major complication rates showed no consistent differences between techniques. Procedure-specific benefits were observed, such as earlier PACU discharge in maxillofacial RA with sedation and reduced intraoperative opioid use in continuous interpectoral block for breast surgery. Conclusions: RA, either alone or combined with GA, provides comparable or improved patient-centred outcomes versus GA alone, with consistent opioid sparing effects and potential reductions in molecular stress markers. While major complication and mortality rates are similar, the choice of anaesthesia should be individualised based on surgical context, patient profile, and ERAS principles.