In this research, a tumor exosome system DOX/2DG@E-RENPs with good biocompatibility, low immunogenicity, and a high targeting effect was proposed for theranostics with high chemo-/starvation/immunotherapy efficiency. DOX and 2-deoxy-D-glucose (DOX/2DG) together with rare earth nanoparticles (RENPs) can be simultaneously carried on the exosome by endocytosis of tumor cells and then exocytosis in vitro. This platform has a good monodispersity with an average size of 70 nm, and the system can emit upconversion luminescence and NIR II luminescence under a single NIR laser. In particular, this exosome can target homing cancer cells and kill the origin tumor cells. The strong targeting effect was proved by different cell lines with exosomes from different orthogonal cells (normal/cancer cells and human/mouse sources, respectively), and the in vivo NIR II imaging guided targeted cancer imaging and liver metastases can be realized by intravenous injection of E-RENPs. Furthermore, the good targeted therapeutic effect and in vivo NIR II imaging and metastases of this platform can be proved. The chemotherapy, starvation therapy, and immunotherapy (immune checkpoint inhibitors of an anti-PD-L1 antibody) could achieve effective synergistic therapy for lung adenocarcinoma, and the immunotherapy can be further proved by the clinical data. This will provide a new strategy for the precise targeting and treatment of tumors.