This study aimed to evaluate whether the Synerjet system can maximize the trans-dermal delivery and skin rejuvenation of nano-NMN. In a 4-week split-face trial (n=21), this combination demonstrated marked clinical superiority over topical nano-NMN alone (p < 0.001), yielding enhanced improvements in wrinkles (170.56% in periorbital and 154.45% in nasolabial, respectively), pore volume (176.62%), and deep hydration (188.02%). Regarding dermal integrity, the test group showed a 111.56% superior increment in skin elasticity and a 149.75% more effective optimization of melanin intensity. Notably, deep-tissue hydration at a 2.5 mm depth demonstrated a 188.02% higher gain, suggesting that the modality significantly fortifies the skin’s physiological moisture reservoir. The test group exhibited a marked improvement over the control across all cutaneous parameters (p < 0.001). Our findings demonstrate that a new combinatorial approach using EP-assisted microjet of Synerjet system after cold plasma pretreatment and a nano-NMN 10% ampoule resulted in significantly greater improvements in wrinkles, pores, elasticity, pigmentation, and deep skin hydration compared to topical application alone. Consequently, these results demonstrated that Synerjet system effectively overcome the inherent lim-itations of nano-delivery technologies, offering a promising modality for advanced cutaneous rejuvenation and a robust framework for future professional dermatological treatments.