Melasma is a refractory facial hyperpigmentary disorder characterized by symmetrical melanosis, with high recurrence rates following conventional single modality treatments. This review examines the mechanisms and clinical potential of combining acupuncture with extracellular vesicles (EVs) therapy. Acupuncture improves local microcirculation, alleviates chronic inflammation, and promotes collagen synthesis through neuroendocrine-immune network regulation. EVs modulate melanocyte function, suppress pro-inflammatory cytokines, and facilitate skin barrier repair via specific microRNAs and protein cargo. The combination creates synergistic effects: acupuncture enhances delivery of EVs and their cellular uptake by optimizing the cutaneous microenvironment, while EVs amplify acupuncture-induced signaling to achieve precise melanogenesis inhibition. Preliminary clinical studies demonstrate superior efficacy in pigment reduction, improved skin texture, and lower recurrence rates compared to monotherapies. This integrative strategy bridges holistic traditional medicine with targeted biotechnological interventions, offering a promising multi-target approach for melasma management.