In recent years, covalent organic frameworks (COFs) have garnered considerable attention in the field of onco-nanotechnology as a new type of nanoporous construct due to their promising physicochemical properties, ease of modification, and ability to be coupled with several moieties and therapeutic molecules. They can not only be used as biocompatible nanocarriers to deliver therapeutic payloads to the tumor zone selectively but can also be combined with a variety of therapeutic modalities to achieve the desired treatments. This review comprehensively presented recent achievements and progress in COF-based cancer diagnosis, detection, and cancer therapy to provide a better prospect for further research. Herein our primary emphasis lies on exploring the application of COFs as potential sensors for cancer-derived biomarkers that have received comparatively less attention in previous discussions. While the utilization of COFs in solid tumor therapy has faced significant challenges in scientific research and clinical applications, we reviewed the most promising features that underscore their potential in cancer theranostics.