Multimodal imaging guided synergistic therapy promises more accurate diagnosis than any single imaging modality, and higher therapeutic efficiency than any single one or their simple "mechanical" combination. Herein, we report a dual-stimuli responsive nanotheranostic based on a hierarchical nanoplatform, composed of mesoporous silica-coated gold nanorods (GNR@SiO2), Indocyanine Green (ICG), and 5-fluorouracil (5-FU), for in vivo multimodal imaging guided synergistic therapy. The 5-FU loaded ICG-conjugated silica-coated gold nanorods (GNR@SiO2-5-FU-ICG) was able to response specifically to the two stimuli of pH change and near-infrared (NIR) light irradiation. Both the NIR light irradiation and acidic environment accelerated the 5-FU release. Meanwhile, the heat generation and singlet oxygen production can be induced by GNR@SiO2-5-FU-ICG upon light irradiation. Most intriguingly, the nanoplatform also promises multimodal imaging such as two-photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy. The cancer theranostic capability of GNR@SiO2-5-FU-ICG was evaluated both in vitro and in vivo. The trimodal synergistic therapy with the guidance of multimodal imaging exhibited remarkably enhanced treatment efficacy. This concept of a hierarchical nanoplatform integrates multiple diagnostic/therapeutic modalities into one platform, which can potentially be applied as personalized nanomedicine with drug delivery, diagnosis, and treatment.