The aim of this study is to develop nanocomposites consisting of near-infrared nanoparticle-functionalized metal-organic frameworks and investigate their antitumor performances. Using molybdenum disulfide and 30% HO as reactants, novel near-infrared molybdenum oxide nanoparticles (HxMoO NPs) were synthesized via supercritical fluid technology. A one-pot method was then employed to synthesize doxorubicin-loaded metal-organic framework nanocomposites and molybdenum oxide nanoparticles (DOX/HxMoO@ZIF-8 NPs). The morphology and structure of the DOX/HxMoO@ZIF-8 were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), and thermogravimetric analysis (TGA). The obtained DOX/HxMoO@ZIF-8 exhibited a uniform crystal structure, high drug-loading of 45.5 mg/g, large specific surface area (311.9 m/g), and excellent photothermal conversion efficiency (79.6%). The in vivo studies showed that mice in the DOX/HxMoO@ZIF-8 + NIR group exhibited the smallest tumor size (22.3 ± 9.2 mm) and the lightest tumor weights (0.02 ± 0.005 g), significantly demonstrating its in vitro and in vivo antitumor activity. These findings suggest that the developed nanocomposite has hight potential for enhancing the application of multifunctional nanocarriers in tumor treatment.