As an E3 ubiquitin-protein ligase, MDM2 is involved in the ubiquitination and subsequent degradation of various proteins, primarily targeting the tumor suppressor protein p53/TP53. By mediating p53's degradation, MDM2 regulates cell cycle progression, apoptosis, and DNA damage repair. In normal cells, MDM2 maintains a delicate balance with p53, jointly modulating cell cycle arrest, apoptosis, and DNA repair to ensure cellular homeostasis. In cancer, MDM2 is frequently overexpressed, leading to increased degradation of p53, thereby inhibiting apoptosis and cell cycle arrest, contributing to tumorigenesis. MDM2 overexpression is also associated with tumor microenvironment remodeling and immune evasion. Furthermore, MDM2 exerts bidirectional effects on CD8+ T cells, CD4+ T cells, and other immune cells like NK cells, DCs, Tregs, and TAMs, shaping the tumor immune microenvironment.