BACKGROUND: Microfocused ultrasound with visualization (MFU-V) and hyperdilute calcium hydroxylapatite-carboxymethylcellulose (CaHA-CMC) dermal injections are effective for improving skin laxity in the lower face and submentum by stimulating neocollagenesis and neoelastogenesis. OBJECTIVES: Combining these treatments in an optimal order may inform best practice in aesthetic dermatology. Despite their frequent concurrent use, no study has evaluated the impact of treatment order. This study aimed to determine the optimal sequence for administering MFU-V and hyperdilute CaHA-CMC. METHODS: Twelve healthy women aged 35 to 65 years were randomized into 2 groups. Group A received MFU-V followed by hyperdilute CaHA-CMC 6 weeks later, while Group B received the treatments in the opposite order. Evaluations included histological assessments, aesthetic outcomes, and safety measures. RESULTS: Group A showed greater improvements in subjective Global Aesthetic Improvement Scale, investigator Global Aesthetic Improvement Scale, and FACE-Q Patient-Perceived Age visual analog scale scores. Both groups exhibited similar improvements in FACE-Q Satisfaction with Lower Face and Jawline scores. Histologically, both groups demonstrated significant elastin production at the 120-day follow-up. Group A showed a 143% relative increase in elastin coverage, compared with a 63% increase in Group B. Consequently, Group A exhibited superior qualitative and histologic improvements. CONCLUSIONS: Administering MFU-V first, followed by hyperdilute CaHA-CMC 6 weeks later, is the optimal sequence for this combination therapy. Although both groups experienced increased elastin synthesis and aesthetic improvements, the order of treatments significantly impacted the outcomes, favoring the sequence used in Group A. This finding provides valuable insight for optimizing combination therapies in aesthetic dermatology.