Background: Excessive submental fat and tissue laxity can significantly impact an individual's aesthetic appearance, leading to cosmetic dissatisfaction and concerns about aging. Non-invasive and minimally invasive treatments have gained popularity as alternatives to surgical interventions. Laser lipolysis, such as EndoliftX®, has emerged as a promising approach for submental fat reduction, and hybrid fillers, like HArmonyCa, have shown potential for enhancing tissue laxity. Objective: This study aimed to evaluate the efficacy and long-term outcomes of a novel combined treatment protocol utilizing laser lipolysis and hybrid filler injection for submental fat reduction and tissue tightening. Methods and Materials: A single-center, prospective, quasi-experimental controlled study was conducted, enrolling seven patients aged between 49 and 67 years. The protocol EndoliftX®, involved a 1470nm diode laser (LASEmaR 1500® Eufoton® Trieste,Italy) treatment (Endolift) followed by hybrid filler (HArmonyCa) injection. Various assessments, including clinical examination, Glogau Scale scoring, and 3D imaging, were performed at baseline and follow-up visits. Results: The results demonstrated significant reductions in submental fat, improved cutaneous elasticity, and reduced wrinkle severity according to the Glogau Scale. Notably, these improvements were visible almost immediately post-procedure and continued to enhance over time, remaining prominent even after 12 months of observation. The treatment was associated with minimal discomfort and downtime. Conclusion: The study highlights the effectiveness and longevity of the combined treatment protocol, making it a valuable option for individuals seeking non-surgical solutions for submental fat reduction and tissue tightening. While further research with control groups is warranted, laser lipolysis with EndoliftX®, and hybrid filler injection with HArmonyCa offer a minimally invasive and well-tolerated approach to address submental concerns and achieve favorable aesthetic outcomes, particularly in patients looking to avoid more invasive techniques.