biomolecules and subsequently induce cancer cell death. [1,4,5] Hydroxyl radicals (•OH) is the most cytotoxic ROS in comparison with other counterparts such as superoxide anions (•O 2 − ), singlet oxygen ( 1 O 2 ), and peroxide (O 2 2−). [6] TME-triggered production of high-level •OH only at tumor sites instead of healthy tissues presents great advantages for anticancer treatments, including low invasiveness, minimal systemic toxicity, high hypoxia-tolerance, and most importantly high tumor specificity. Utilizing the features of abundant H 2 O 2 (typically ranging from 100 µm to 1 mm) and low catalase activity in the TME, in situ Fenton or Fenton-like reactions between transition metal ions (e.g., Fe 2+ , Mn 2+ , Cu + ) and intracellular H 2 O 2 produce •OH only at tumor sites, with negligible damage to healthy tissues. [7][8][9] Recent studies also showed that Fenton reactions with improved •OH generation efficiency could be achieved by either increasing the local tumor temperature or using light irradiation. [10,11] To further promote anticancer effects, "all-in-one" phototheranostic platforms combining diagnostic and therapeutic capabilities into a single entity have been developed by integrating ROS-based CDT with other therapeutic modalities (e.g., photodynamic therapy (PDT), chemotherapy, immunotherapy, photothermal therapy (PTT)), together with imaging modalities such as photoacoustic (PA) imaging, photothermal (PT) imaging, fluorescence imaging, magnetic resonance imaging, and computed topography (CT). [12][13][14][15][16][17][18] A successful marriage of these imaging and therapeutic modalities would yield bioimaging-guided on-demand cancer treatments with real-time tumor visualization, high controllability, low sideeffects, and excellent therapeutic efficacy.Despite those considerable advances, two critical issues still hinder clinical translation of ROS-mediated phototheranostic platforms that integrate photo-Fenton reaction involved CDT/ PDT, PTT, and optical imaging modalities. First, most of those previous "all-in-one" phototheranostic agents typically request multiple different laser wavelengths to implement imagingguided cancer treatments, which significantly increases the complexity and total cost of cancer treatments. [19,20] Second, Tumor microenvironment (TME)-activatable phototheranostics is highly desirable in cancer management but still remains challenging for clinical applications owing to the lack of multifunctional theranostic agents and the limited tissue penetration depth. Reported here is an "all-in-one" phototheranostic platform based on near-infrared II (NIR-II) dual-plasmonic Au@Cu 2−x Se core-shell nanocrystals (dpGCS NCs) for combined photoacoustic (PA)/photothermal (PT) imaging-guided chemodynamic therapy (CDT)/ photocatalytic therapy (PCT)/photothermal therapy (PTT) all triggered by a single NIR-II laser. The dpGCS NCs feature excellent NIR-II plasmonic and PT properties, which guarantee their capabilities of NIR-II PA and PT imaging for real-time visual observation of tumor si...