Despite the advantages of high tissue penetration depth, selectivity, and non‐invasiveness of photothermal therapy for cancer treatment, developing NIR‐II photothermal agents with desirable photothermal performance and advanced theranostics ability remains a key challenge. Herein, a universal surface modification strategy is proposed to effectively improve the photothermal performance of vanadium carbide MXene nanosheets (L‐V2C) with the removal of surface impurity ions and generation of mesopores. Subsequently, MnOx coating capable of T1‐weighted magnetic resonance imaging can be in situ formed through surface redox reaction on L‐V2C, and then, stable nanoplatforms (LVM‐PEG) under physiological conditions can be obtained after further PEGylation. In the tumor microenvironment irradiated by NIR‐II laser, multivalent Mn ions released from LVM‐PEG, as a reversible electronic station, can consume the overexpression of glutathione and catalyze a Fenton‐like reaction to produce ·OH, resulting in synchronous cellular oxidative damage. Efficient synergistic therapy promotes immunogenic cell death, improving tumor‐related immune microenvironment and immunomodulation, and thus, LVM‐PEG can demonstrate high accuracy and excellent anticancer efficiency guided by multimodal imaging. As a result, this study provides a new approach for the customization of 2D surface strategies and the study of synergistic therapy mechanisms, highlighting the application of MXene‐based materials in the biomedical field.