Chronic wounds arise from a combination of factors, including impaired macrophage and fibroblast function, dysregulated cytokine signaling, and insufficient angiogenesis. Non-healing wounds, including diabetic foot ulcer, venous leg ulcer resulting from peripheral artery disease or critical limb ischemia, remain a significant and growing healthcare challenge, particularly in aging populations. Existing treatments often fail to address these multifactorial conditions. Although stem cell-based therapies show promising results, several challenges remain related to consistent cell sourcing, scalable expansion techniques, optimized delivery strategies, universally accepted protocols for cell characterization, and potency testing. Recent research has shifted toward exploring stem-cell-derived extracellular vesicles (EVs) as carriers of bioactive factors. EVs exhibit high tissue-targeting ability, biocompatibility, stability in circulation, and low immunogenicity. Their therapeutic functions include modulation of immune responses and inflammation, stimulation of angiogenesis, acceleration of cell proliferation, and regulation of collagen remodeling, making them suitable for regenerative medicine. Nevertheless, current preclinical studies show poor reproducibility in animal models, and limited clinical data exist regarding EV efficacy. Overall, stem cell and EV-based therapies hold transformative potential for chronic wound care. Multidisciplinary collaboration will be necessary for these biological therapies to become integral components of personalized, effective, and accessible treatment strategies for patients with chronic, non-healing wounds.