The restoration of cutaneous tissue integrity following injury is a temporally orchestrated and biologically complex process, underpinned by a dynamic interplay among blood-borne immune cells, resident stromal and epithelial cells, soluble mediators, and extracellular matrix remodeling. Recent advances in nanobiology have highlighted the pivotal role of cell-specific endosome-originated small extracellular vesicles (sEV), also known as exosomes, as fundamental mediators of intercellular communication. These sEV facilitate the targeted transfer of bioactive cargos, including regulatory ribonucleic acid (RNAs), proteins, and lipids, which are instrumental in key reparative processes such as inflammation resolution, angiogenesis, and epithelial regeneration. In this chapter, we critically evaluate the emerging functions of sEV in cutaneous wound healing, elucidating their mechanistic roles and therapeutic potential. We delineate a series of bidirectional and tripartite signaling circuits between resident cells and infiltrating immune cells for effective tissue restitution. Disruption of these sEV-mediated exchanges leads to the pathophysiology of chronic, nonhealing wounds, characterized by persistent inflammation, fibroblast dysfunction, and epithelial staling. Concurrently, we investigate how bacterial outer membrane vesicles (OMVs) utilize the structural and functional mimicry of host exosomes to subvert regenerative signaling, amplify local inflammation, and facilitate biofilm formation, thereby making the bacteria recalcitrant to antimicrobial therapy. These microbial vesicles engage in sophisticated interkingdom communication, thereby reshaping the wound microenvironment to favor chronicity and immune evasion. Finally, we explore the translational trajectory of bioengineered exosomes and synthetic sEV mimetics as emerging nanotherapeutic platforms. These vesicles are being strategically engineered to exhibit enhanced cellular tropism, extended systemic persistence, and stimulus-responsive release kinetics. By incorporating precision cargos such as small interfering RNAs (siRNAs), microRNAs (miRNAs), Clustered Regularly Interspaced Palindromic Repeats–associated protein (CRISPR-Cas9) gene-editing components, and immunomodulatory proteins, these next-generation vesicular systems hold significant promise for the targeted modulation of pathological signaling pathways in chronic wounds and for advancing cell-specific regenerative interventions.