Construction of innovative nanomedicine with bioderived molecules is of great research interest to achieve effective cancer treatment owing to their intrinsic biocompatibility and biodegradability. By virtue of their intrinsic physiochemical properties, tremendous natural phenolic molecules and their synthetic derivatives have been explored for the construction of diverse functional materials including nanomedicine. In this review, we firstly make a summary on approaches (e.g., oxidative polymerization, metal-phenolic network formation) commonly utilized for the construction of diverse nanomedicine with unique properties by using these phenolic molecules as the building blocks. Later, the applications of these engineered nanomedicine in photothermal therapy, tumor targeted delivery of therapeutic ions, small molecules, and biomacromolecules, as well as tumor microenvironment modulation will be described in detail. Finally, future perspectives on the construction of these phenolic molecules based nanomedicine and their potential clinical translation will be provided.