<p>Globally, chronic wounds affect over 40 million patients, reducing patient quality of life and exerting a significant and growing burden on healthcare systems. Effective healing is often hindered by conventional wound dressings, particularly in complicated cases involving infection, biofilm, or impaired tissue regeneration. In response, nanofiber mats, electrospun to accurately mimic the extracellular matrix (ECM), have emerged as a transformative platform for advanced wound care accordingly. Inefficient trial-and-error approaches have nevertheless been employed in their development, leading to inconsistent performance and protracted development timelines. As a result, this article reports a significant change in the development of sustainable nanofiber-based wound dressings through the integration of artificial intelligence (AI) and quality by design (QbD). We discuss how QbD employs process optimization and structured risk assessment to ensure consistent, reproducible quality products, and how AI accelerates formulation design, predicts performance, and enables real-time monitoring. We further emphasize the significance of biodegradable polymers, green manufacturing processes, and data-driven customization in creating scalable, patient-specific, and environmentally sustainable solutions. Where nanotechnology, QbD, and AI meet, a new generation of intelligent, sustainable, and wound care technology is introduced that enhances long-term health outcomes and overall well-being worldwide.</p> Graphical Abstract <p></p>