Multifunctional nanoplatforms with multimodal imaging and cancer therapy capabilities have attracted attention in biomedical applications. Near-infrared persistent luminescence nanoparticles (NPLNPs) were considered one of the most promising candidates for constructing multifunctional nanoplatforms due to the absence of in situ excitation and high signal-to-noise ratios (SNRs). Here, we report a novel NPLNP mSiO₂@Gd₃Ga₅O₁₂:Cr³⁺, Nd³⁺ (mSiO₂@GGO) as multifunctional nanoplatforms for multimodal imaging and cancer therapy. These NPs exhibited a persistent luminescence (745 nm) of more than 3 h in the first near-infrared window (NIR-I) after UV excitation, which can realize high SNRs and long-term in vivo imaging. Moreover, these NPs showed excellent NIR luminescence (1067 nm) in the second near-infrared window (NIR-II) under 808 nm excitation, which is more suitable for deep tissue imaging due to the lower photon scattering and deeper tissue penetration of NIR-II luminescence. Furthermore, the host Gd₃Ga₅O₁₂ with high Gd³⁺ concentration showed a high r₁ value (10.70 mM⁻¹ s⁻¹) and was suitable for T₁ MR imaging. The mesoporous silica nanoparticles (mSiO₂) served as a framework to control the mSiO₂@GGO particle morphology and provide low toxicity and drug loading capacity for cancer therapy.