Melasma is a benign skin condition characterized by hyperpigmented patches, primarily affecting the face, and significantly reducing patients' quality of life. Treatment is challenging due to its recurrent nature, with no single modality proving universally effective. The combination of Q-switched Nd:YAG laser treatment and FOB® Tri-White Serum (Hong Nhung Cosmetics Co., Ltd., Can Tho, Vietnam) may represent a promising new therapeutic approach. This cross-sectional descriptive study involved 85 female patients with melasma treated at two dermatological centers between July 2023 and June 2024. Patients underwent four Q-switched Nd:YAG laser sessions (1064 nm, 1.5-1.7 J/cm2) at three-week intervals and applied FOB® Tri-White Serum twice or three times daily. Treatment effectiveness was assessed using the Melasma Area Severity Index (MASI) score and the Felix Von Luschan skin color chart. Data were analyzed using Stata 17.0 MP, with p<0.05 considered statistically significant. The mean MASI score improved significantly from 7.5±4.7 to 4.9±3.5 (p<0.05), with a 69.4% response rate. Younger patients (<45 years), individuals with a shorter disease duration (≤36 months), and cases of mild to moderate melasma exhibited more favorable outcomes. Adverse effects from both the laser and serum were mild and transient. The combination of Q-switched Nd:YAG laser and FOB® Tri-White Serum is a safe and effective treatment for melasma, demonstrating significant improvement in pigmentation with minimal side effects. Further research is needed to validate these findings with larger sample sizes and control groups.