Background <p>Burn injuries cause severe physical and psychological challenges. Current treatments have limitations, such as incomplete skin regeneration and prolonged healing times, necessitating innovative solutions. Tissue engineering integrates mesenchymal stem cells (MSCs) and scaffolds in preclinical studies to enhance healing, reduce scarring, and regenerate skin. This study examines their combined effects to optimize burn wound therapies.</p> Methods <p>This systematic review and meta-analysis was conducted per PRISMA guidelines, with the protocol registered in PROSPERO. Databases (PubMed, Embase, Scopus, Web of Science, ProQuest) were searched for published studies.The SYRCLE tool assessed risk of bias. Standardized mean difference (SMD) evaluated the therapeutic effect of MSC-scaffold combinations. Statistical analysis employed a random-effects model. Sensitivity analysis, publication bias assessment, and subgroup analysis addressed heterogeneity.</p> Results <p>Our meta-analysis reveals that animals treated with MSC-scaffold combinations exhibit enhanced wound closure compared to untreated controls across short-term (SMD = 3.97), mid-term (SMD = 3.47), and long-term (SMD = 3.03) timeframes. Additionally, MSC-scaffold combinations significantly improve angiogenesis (SMD = 6.24), collagen deposition (SMD = 4.97), and growth factor expression (SMD = 6.68), while effectively modulating inflammatory cytokine levels (SMD = -4.88).</p> Conclusion <p>Our research demonstrates that MSC-scaffold synergy in preclinical burn wound healing significantly improves wound closure, collagen deposition, angiogenesis, and growth factor expression, while effectively modulating inflammatory responses. Despite its potential as an adjunctive therapy, substantial study heterogeneity impedes clinical translation, necessitating standardized protocols to refine and validate this approach for efficacious clinical application.</p> Graphical Abstract <p></p>