Metal–organic frameworks (MOFs) are an interesting and useful class of coordination polymers, constructed from metal ion/cluster nodes and functional organic ligands through coordination bonds, and have attracted extensive research interest during the past decades. Due to the unique features of diverse compositions, facile synthesis, easy surface functionalization, high surface areas, adjustable porosity, and tunable biocompatibility, MOFs have been widely used in hydrogen/methane storage, catalysis, biological imaging and sensing, drug delivery, desalination, gas separation, magnetic and electronic devices, nonlinear optics, water vapor capture, etc. Notably, with the rapid development of synthetic methods and surface functionalization strategies, smart MOF‐based nanocomposites with advanced bio‐related properties have been designed and fabricated to meet the growing demands of MOF materials for biomedical applications. This work outlines the synthesis and functionalization and the recent advances of MOFs in biomedical fields, including cargo (drugs, nucleic acids, proteins, and dyes) delivery for cancer therapy, bioimaging, antimicrobial, biosensing, and biocatalysis. The prospects and challenges in the field of MOF‐based biomedical materials are also discussed. The synthesis and functionalization of metal–organic frameworks (MOFs) for biomedical applications in the delivery of cargos (drugs, nucleic acids, proteins, and dyes) for cancer therapy, bioimaging, antimicrobial, biosensing, and biocatalysis are overviewed, and the development prospects and challenges of MOF‐based theranostic systems are also discussed.