In this study, a fascinating nanoplatform, possessing fluorescent imaging, hyperthermia-amplified reactive oxygen species (ROS) generation, and calcium-overloaded comediated multimodal therapeutic effects toward breast malignancy, was innovatively constructed. Accordingly, engineering this accurate targeting theranostic scheme can be used for efficacious ablation of breast carcinoma. Because Cu and Ca ions can induce ROS generation and cytoplasmic overaccumulation, respectively, here, a Cu−Ca-based nanoplatform was designed by adsorbing indocyanine green (ICG) through the relatively high specific surface area and Arg-Gly-Asp peptide (RGD) decorating by covalent conjugation. Upon the internalization of breast tumor cells, biodegradation was triggered under an intracellular weak acid microenvironment; the released ICG molecules allowed for near-IR (NIR) II fluorescent imaging and photothermal production. Importantly, Cu ions in the nanoplatform guaranteed more efficient Fenton-like reaction-mediated chemodynamic therapy under NIR laser exposure. Meanwhile, the virus-like hollowed Cu−Ca (VhCu-Ca) nanoplatform created an artificial calcium-overloading stress in the cytoplasm. In vitro and in vivo studies have demonstrated that our proposed Cu−Ca-based nanoplatform integrated the advantages of breast tumor targeting, NIR II fluorescent imaging, and efficient ablation via synergistic treatments. Therefore, this multimode nanoplatform developed a facile and versatile strategy for the diagnosis and suppression of breast tumors.