Despite the widespread applications of manganese oxide nanomaterials (MONs) in biomedicine, the intrinsic immunogenicity of MONs is still unclear. Herein, MnOx nanospikes (NSs) as tumor microenvironment (TME)-responsive nanoadjuvants and immuogenic cell death (ICD) drugs are proposed firstly for cancer nanovaccine-based immunotherapy. MnOx NSs with large mesopores structures show ultrahigh loading efficiencies for ovalbumin and tumor cell fragment. The combination of ICD via chemodynamic therapy and ferroptosis inductions as well as antigen stimulations presents a better synergistic immunopotentiation action. Furthermore, the obtained nanovaccines can not only achieve TME-responsive magnetic resonance/photoacoustic dual-mode imaging contrasts, but also effectively inhibit primary/distal tumor growth as well as tumor metastasis.