Abstract: Atherosclerosis is a chronic inflammatory disease, and vascular smooth muscle cells (VSMC) play a central role in its pathological process. Single-cell RNA sequencing reveals the central role of VSMC in the atherosclerotic microenvironment. Inflammatory factors and oxidized lipids in the atherosclerotic plaque microenvironment affect VSMC phenotype switching and function in various ways, thereby affecting plaque stability. This article summarizes the phenotypic transformation rules, biological behaviors, and interaction mechanisms of VSMC with immune cells in the inflammatory microenvironment of atherosclerosis, and reviews the progress of new anti-inflammatory strategies and models targeting the VSMC-inflammatory axis, in order to provide a theoretical basis and translational direction for the precise treatment of atherosclerosis.