Precisely locating tumor site based on tumor-microenvironment-induced (TMI) multimodal imaging is especially interesting for accurate and efficient cancer therapy. In the present investigation, a novel TMI all-in-one nanoplatform, CuS@DOX@MnO, has been successfully fabricated for chemical and photothermal (Chem-PTT) therapy guided by multimodal imaging on tumor site. Here, the CuS nanocages with mesoporous and hollow structure (CuS) acting as nanocarriers provide high capacity for loading the anticancer drug, doxorubicin (DOX). The outer layer of the MnO nanoshell (MnO) acts as "gatekeeper" to control the DOX release until the nanoplatform arrives at the tumor site, where abundant glutathione and H decompose MnO into paramagnetic Mn. The magnetic resonance imaging and fluorescent imaging were then triggered to locate the tumor, which was further improved by photothermal imaging on account of the intrinsic property of CuS. Guided by the multimode imaging, the combination of chemical therapy upon DOX and photothermal therapy upon CuS exhibits eminent efficiency on tumor ablation. The nanoplatform exhibits biocompatibility to avoid unwanted harm to normal tissues during trans-shipment in the body. The investigation thus develops a cost-effective TMI nanoplatform with facile preparations and easy integration of Chem-PTT treatment capabilities guided by multimodal imaging for potential application in precise therapy.