Very different from traditional inside-out method, which used guest material as the inside core and then surfacecoated outer layer, herein, we propose a facile and unique outside-in approach for the synthesis of high dispersive mesoporous silica nanoparticle (MSN)/MoS2-PEG nanoparticles (SMPs) based on the differences of precursor solubility in different solvents, for the first time. The prepared SMPs exhibit both higher drug loading efficiency of 64.7% owing to the pore structure of mesoporous silica, and excellent photothermal performance with photothermal efficiency of 41.5% due to the inside decorated MoS2 nanosheets, which could be used for the combination of tumor hyperthermia and chemotherapy. The in vivo results indicate that SMPs show great synergistic effect, i.e., the heat produced during PTT can increase the chemotherapy sensitivity of DOX and synergistically improve its therapeutic effect. Such a facile strategy provides a new facile way to construct a novel theranostic agent by integrating different functions into one dosage, and shows a promising approach for the construction of nanomaterials using MSN as a template.