Background <p>Composite grafts remain a vital reconstructive option for complex facial defects involving cartilage and skin, yet their viability is often limited by poor vascularization. Ghrelin, a gastric hormone with demonstrated anti-inflammatory and pro-angiogenic properties, and adipose-derived mesenchymal stem cells (AD-MSCs) may represent novel adjuncts to enhance graft survival.</p> Methods <p>Thirty-five Wistar-Albino rats were divided into five groups: control, placebo, ghrelin, AD-MSC, and combination (ghrelin + AD-MSC). A standardized 1 × 1&#xa0;cm chondrocutaneous graft was harvested from the left ear and inset into a subcutaneous dorsal pocket. Respective agents were administered locally at the recipient site. Graft survival was evaluated macroscopically and histologically on postoperative day 7. Immunohistochemistry for vascular endothelial growth factor (VEGF) and histological scoring were performed.</p> Results <p>The combination of ghrelin and AD-MSCs significantly improved graft survival compared to control and placebo groups (<i>p</i> &lt; 0.05). Histological analysis showed increased angiogenesis (VEGF expression) and reduced inflammatory cell infiltration. The highest graft survival and vascularization scores were observed in the combined treatment group.</p> Conclusions <p>Both ghrelin and AD-MSCs enhance composite graft viability individually, but their combined use yields synergistic benefits in angiogenesis and graft survival. These findings support the potential application of ghrelin and stem cell therapies in composite tissue reconstruction, especially in aesthetically sensitive facial areas.</p> Level of Evidence <p>Not gradable.</p>