The emergence of horizontal neck wrinkles is increasingly becoming a focal point for both cosmetic professionals and clients. Various treatment approaches must be considered to address this issue effectively, owing to its diverse underlying causes. The study explores the potential of utilizing the Endolift laser in conjunction with nanofat injection as a viable treatment option. Twenty patients with horizontal neck wrinkles involved in the study. Ten patients underwent treatment with a combination of Endolift laser and nanofat injection and 10 patients treated with nanofat injection alone. The participants were monitored for 6 months post-treatment. Biometric measurements were utilized to assess outcomes, including changes in volume, depth, and area of the wrinkles, skin elasticity, as well as the diameter and density of the epidermis and dermis in the treated area. Skin improvement was evaluated by two independent dermatologists, who compared before and after photos in a blinded manner. Patient satisfaction levels were also documented. The Visioface analysis showed a notable decrease in neck wrinkle depth and area in both groups. However, the group receiving the combination treatment of Endolift laser and nanofat exhibited a significantly greater improvement compared to the group treated with nanofat alone. Skin ultrasonography results demonstrated an increase in thickness and density of the dermis and epidermis in both groups. Particularly, the group treated with Endolift laser-nanofat displayed significant enhancements in dermis and epidermis density and thickness when contrasted with the nanofat-only group. Analysis with Cutometer revealed a marked enhancement in skin elasticity in the Endolift-nanofat treated group in comparison to the nanofat-only treated group. Furthermore, in the Endolift-nanofat treated group, a substantial majority (90%) of patients exhibited improvement. Patient evaluations highlighted significant distinctions between the two groups, with 95% of patients in the Endolift-nanofat treated group demonstrating enhancement. Both methods notably enhance horizontal neck wrinkles; nevertheless, the combination of endolift laser and nanofat seems to be more efficient for treating horizontal neck wrinkles.