Chemodynamic therapy (CDT) is seriously limited by the inadequacy of exogenous catalytic ions and endogenous HO in tumors. Herein, a multifunction nano-bomb integrated with calcium peroxide (CaO) and β-lapachone as donors of HO and GSH-sensitive Fe-based coordination polymer as provider of catalytic ions was constructed for dual cascade-amplified tumor CDT. This hyaluronic acid (HA)-modified nano-bomb could be specially endocytosed by breast cancer cells through a targeting pathway, degraded and released cargoes in response to the GSH-rich cytoplasm. Furthermore, the released CaO and β-lapachone could significantly self-generated sufficient HO, which could dual-cascade amplify CDT and induce severe oxidative to tumors via cooperating with the delivered iron ions from nano-bombs. Moreover, the unloaded iron and calcium ions could further accelerate tumor damage by overloading Ca and ferroptosis, as accompanied by good magnetic resonance imaging (MRI). In vitro and in vivo studies collectively reveal that this nano-bomb not only self-initiates double cascade-amplified CDT via self-generation of HO, but also efficiently activates ferroptosis and initiates Ca overloading, consequently significantly tumor growth suppression. This study offers a novel tumor-initiated nano-bomb for dual cascade-amplified CDT and bioimaging with activated ferroptosis and self-supplying HO.