Cancer has become one of the main causes of death worldwide. Chemotherapy as one of the main therapy modalities is very unsatisfactory. The various nanocarriers have brought new opportunities for effective tumor treatment. However, most of the current nanocarriers still suffer from low efficiency and confront significant challenges in overcoming multiple biological barriers. Compared with conventional nanocarriers, covalent organic frameworks (COFs) with unique and attractive features exhibited great potential to serve as a promising platform for anticancer drug delivery. In this review, we first summarize the strategies and challenges of nanocarriers for cancer chemotherapy and then highlight the recent advances in COF-based nanocarriers for improved delivery of chemotherapeutic agents. Finally, the challenges remaining for COF-based nanocarriers for clinical applications are outlined.