Skin tissue engineering, a critical area within regenerative medicine, focuses on creating functional replacements for damaged or diseased skin. Electrospray ionization has emerged as a promising method in this field due to its precision in biomaterial and bioactive molecule deposition. This chapter discusses electrospray’s role in revolutionizing scaffold fabrication, cell encapsulation, and therapeutic delivery in skin engineering. Electrospray allows for the production of scaffolds that mimic the skin’s extracellular matrix, enhancing cell adhesion, proliferation, and differentiation. It also enables efficient encapsulation of growth factors, promoting sustained release at targeted sites to improve wound healing and skin regeneration. Electrospray-assisted fabrication of scaffolds has shown superior biocompatibility and structural features over traditional methods. Furthermore, the technology’s capability for directing cell and therapeutic delivery to wound sites introduce personalized treatment options for various skin conditions, making a significant advancement toward the clinical use of engineered skin tissues.