Nanomedicines are extensively used in cancer therapy. Covalent organic frameworks (COFs) are crystalline organic porous materials with several benefits for cancer therapy, including porosity, design flexibility, functionalizability, and biocompatibility. This review examines the use of COFs in cancer therapy from the perspective of reticular chemistry and function‐oriented materials design. First, the modification sites and functionalization methods of COFs are discussed, followed by their potential as multifunctional nanoplatforms for tumor targeting, imaging, and therapy by integrating functional components. Finally, some challenges in the clinical translation of COFs are presented with the hope of promoting the development of COF‐based anticancer nanomedicines and bringing COFs closer to clinical trials. The exceptional customizability of covalent organic frameworks (COFs) has attracted significant interest for function‐oriented materials design. Recent advances in functionalization strategies and constructing COF‐based therapeutic nanoplatforms for cancer therapy are highlighted, and some challenges in the clinical translation of COFs are discussed to promote the development of COF‐based anticancer nanomedicines.