Background: Mechanical forces play a crucial role in regulating cellular communication during tissue repair, yet how mechanical stimulation modulates endothelial exosome secretion and their effects on fibroblast activation remains unclear. Methods: In this study, endothelial cells were incorporated into 3D bioprinted tissue-engineered dermal constructs and cultured under static or mechanically stretched conditions. Exosomes were isolated, characterized, and applied to human dermal fibroblasts to assess their influence on proliferation, migration, and extracellular matrix formation. Data-independent acquisition proteomics was performed to analyze exosomal protein cargo and associated signaling pathways. Results: Mechanical loading increased exosome secretion by approximately 2.5-fold without altering vesicle morphology. Functionally, mechanically stimulated exosomes significantly enhanced fibroblast migration and type I collagen synthesis compared with controls. Proteomic profiling identified 4,476 proteins, of which 677 were differentially expressed. Enrichment analysis revealed activation of VEGF, HIF-1, Relaxin, and AGE–RAGE pathways, implicating roles in angiogenesis, metabolic regulation, and extracellular matrix remodeling. Conclusion: These findings demonstrate that 3D mechanical stimulation not only augments the quantity of endothelial exosomes but also reshapes their molecular cargo, thereby enhancing biomechanical communication between endothelial cells and fibroblasts. Together with prior evidence of fibroblast-derived exosomes promoting endothelial angiogenesis, this study proposes a bidirectional “mechanical stimulation–exosome–communication–tissue reconstruction” loop, providing a theoretical foundation for optimizing exosome-based strategies in skin tissue engineering.