The development of efficient drug delivery systems is essential for improving the efficacy and safety of cancer drugs, particularly for aggressive and difficult‐to‐treat cancers. Covalent organic frameworks (COFs) are emerging as innovative porous nanomaterials in drug delivery systems (DDS), due to their unique properties, including the metal‐free organic skeleton, predetermined structures and pore geometries, high porosity, large surface area, facile surface modification potential, and good biocompatibility. These characteristics make COFs excellent candidates for improving drug delivery by enhancing drug loading capacity and enabling precise encapsulation. This review emphasizes the importance of donor‐acceptor‐based COFs, which provide channels for charge transportation, and we also explore how the π‐conjugated skeleton of COFs enhances its long‐acting fluorescent properties and facilitates drug uptake via cell endocytosis. While this review primarily focuses on recent advancements in COF‐based targeted DDS, it also acknowledges the challenges posed by the diverse pore geometries in porous materials and discusses potential solutions. Further, it underlines the potential of developing future drug carriers that can successfully and specifically target cancer cells, improving treatment efficiency while reducing adverse side effects.