AbstractChemodynamic therapy (CDT) is a particular oncological therapeutic strategy by generates the highly toxic hydroxyl radical (•OH) from the dismutation of endogenous hydrogen peroxide (H2O2) via Fenton or Fenton‐like reactions. However, single CDT therapies have been limited by unsatisfactory efficacy. Enhanced chemodynamic therapy (ECDT) triggered by near‐infrared (NIR) is a novel therapeutic modality based on light energy to improve the efficiency of Fenton or Fenton‐like reactions. However, the limited penetration and imaging capability of the visible (400–650 nm) and traditional NIR‐I region (650–900 nm) light‐amplified CDT restrict the prospects for its clinical application. Combined with the high penetration/high precision imaging characteristics of the second near‐infrared (NIR‐II,) nanoplatform, it is expected to kill deep tumors efficiently while imaging the treatment process in real‐time, and more notably, the NIR‐II region radiation with wavelengths above 1000 nm can minimize the irradiation damage to normal tissues. Such NIR‐II ECDT nanoplatforms have greatly improved the effectiveness of CDT therapy and demonstrated extraordinary potential for clinical applications. Accordingly, various strategies have been explored in the past years to improve the efficiency of NIR‐II Enhanced CDT. In this review, the mechanisms and strategies used to improve the performance of NIR‐II‐enhanced CDT are outlined.