ABSTRACT The skin functions as the body's primary barrier against external environmental insults, rendering it particularly susceptible to injury and in need of effective wound management strategies. To date, metal–organic framework (MOF)‐based biomaterials, mainly composed of metal ions or clusters coordinated with organic ligands, have offered exceptional advantages in wound dressing biomaterials due to their biocompatibility, high porosity, tunable structure, and intrinsic multifunctionality, enabling controlled drug delivery, stimuli‐responsive behavior, and potent antimicrobial activity. However, investigations into their additional therapeutic potentials beyond antibacterial effect — e.g., immunomodulation, anti‐inflammatory effects, promotion of angiogenesis, and facilitation of skin‐nerve repair — remain comparatively limited. These biological effects are believed to arise through multiple mechanisms, including the intrinsic catalytic activities of MOFs, their capacity for controlled drug delivery, and the bioactive functions of their constituent metal ions and organic ligands. This review aims to provide a comprehensive overview of the multifaceted roles of MOF‐based biomaterials in wound healing, encompassing not only their antibacterial activities but also their clarified and potential mechanisms in immune regulation, vascularization, and neural regeneration. By elucidating these mechanisms, we seek to advance the understanding of MOF‐based biomaterials in skin tissue regeneration and offer a theoretical foundation to guide future development and optimization of MOF‐based biomaterials for clinical applications.