MoS₂/TiO₂ nanostructures made of MoS₂ nanoparticles covering TiO₂ nanosheets have been synthesized, either via ex-situ or in-situ approaches. Morphology and structure of MoS₂/TiO₂ hybrid nanostructures have been investigated and imaged by means of X-ray diffraction (XRD) analysis and high-resolution transmission electron microscopy (HRTEM), while the vibrational and the optical properties have been investigated by Raman, Fourier-transform infrared spectroscopy (FTIR) and UV−visible (UV-Vis) techniques. The different stacking degrees together with the size distribution of the MoS₂ nanosheets, decorating the TiO₂ nanosheets, have been carefully obtained from HRTEM images. The nature of the surface sites on the main exposed faces of both materials has been detected by means of in-situ FTIR spectra of adsorbed CO probe molecule. The results coming from the ex-situ and in-situ approaches will be compared, by highlighting the role of the synthesis processes in affecting morphology and structure of MoS₂ nanosheets, including their curvature, surface defects, and stacking order. Some more, it will be shown that the in-situ approach is affecting the reactivity of the TiO₂ nanosheets too, hence in turn affects the MoS₂/TiO₂ nanosheets interaction.