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Objectives: The aim of this case series is to assess the efficacy and safety of combining high-intensity microfocusing ultrasound (mHIFU) with thermal diffusion technology (TDT), dermal PDRN and skin booster injections, and exosomes for facial skin tightening and rejuvenation in Asian-skinned patients. Previous studies have demonstrated individual effects of HIFU, PDRN, skin boosters, and exosomes in treating a wide array of anti-aging, anti-inflammatory, and regenerative concerns. Introduction: Anti-aging is a top reason for visit in aesthetic clinics. Multiple factors lead to aging skin and an overall tired and sad look. Hesitancy toward surgical procedures leads patients to look for non-invasive procedures that offer less downtime, while still having favorable outcome. Advances in technology led to mHIFU with TDT in line and pen transducer forms, offering a more precise and comfortable treatment. PDRN, skin boosters, and exosomes are well-known for anti-inflammatory and regenerative properties. Combination of these treatments is promising in delivering effective long-term results. Materials / method: The case series was done in a single center, with 30 patients: 25 female, 5 male, aged 31-73. Patients had Fitzpatrick skin type IV (83%) and III (17%). Patients underwent a single session of the combined treatment. Patients underwent mHIFU at 4.5mm, 3mm, and 1.5mm depths for the face and neck. Shot count per depth was 300 for line, and 1500 for pen transducers. A concoction of PDRN and skin booster (hyaluronic acid, amino acids) was then injected 1.2mm via multi-suction injector, followed by topical exosomes. Photographs and Visia skin analysis were taken before and 3 months post-treatment. Results: Combination of mHIFU with PDRN concoction injection, and exosomes application resulted in wrinkle score decrease by 1 (i.e, from 3 to 2; 2 to 1) on the Modified Fitzpatrick Wrinkle Scale. Global aesthetic improvement scale rated by 2 independent investigators at 3 months post-treatment showed 57% with much improvement, 43% with improvement of overall skin quality. Patients rated their satisfaction from 1-5 (1-extremely not satisfied, 5-extremely satisfied), with an average of 4.4. Visia parameters (pores, texture) also improved. Treatment was well-tolerated. No significant side effect reported Conclusion: Combination of these treatments is a safe and effective treatment for facial skin tightening and rejuvenation in Asian skin. The combination may be advantageous because of the compounding synergistic effects of each of the modalities. mHIFU with TDT induced controlled and precise microinjuries on the skin, PDRN with skin booster injections enhances cellular repair, remodelling, and collagen production, and exosomes made the healing process faster. Patient selection remains to be the essential in recommending treatment combinations to achieve the most satisfactory results and improvement.