In this study, a multifunctional tumor microenvironment (TME)‐responsive nanocomposite is constructed using manganese tetroxide (Mn3O4)‐decorated disulfide‐bond‐incorporated dendritic mesoporous organosilica nanoparticles (DMONs) to co‐deliver indoleamine 2,3‐dioxygenase (IDO) inhibitor Epacadostat (IDOi) and glucose oxidase (GOx) following modification with polyethylene glycol. The gene discussed is IDO2; the disease is neoplasm.