Artificial nanoscale enzyme-mimics (nanozymes) are promising functional alternatives to natural enzymes and have aroused great interest due to their inherent stability, affordability, and high catalytic ability. Iron-based nanozymes are one of the most investigated synthetic nanomaterials with versatile enzyme-like catalytic properties and have demonstrated remarkable relevance to a variety of biomedical applications, especially biocatalytic therapy against tumor indications. Nevertheless, despite the recent advances in biology and nanotechnology, the therapeutic performance of iron-based nanozymes is still limited by technical issues such as low catalytic efficiency and lack of tumor specificity. In this mini review, we briefly summarized the representative studies of iron-based nanozymes, while special emphasis was placed on the current challenges and future direction regarding the therapeutic implementation of iron-based nanozymes for the development of advanced tumor therapies with improved availability and biosafety.