The realization of polymeric nanocomposites is a promising strategy for large-scale applications of photocatalytic nanomaterials, limiting their dispersion into the environment. In addition, in order to obtain very efficient materials, a valid solution can be the formation of heterojunctions that, reducing the electron-hole recombination phenomena, increases the performances of the photocatalysts. For this work, we have realized promising photocatalytic polymeric nanocomposites through the simple method of sonication and solution casting, using poly (methyl methacrylate)(PMMA) as supporting matrix, ZnO nanoparticles as photoactive material, and MoS2 nanoflakes as co-catalyst for the realization of the heterojunction. Materials with several quantities of MoS2 have been synthetized and characterized by scanning electron microscopy (SEM), contact angle measurements, X-ray diffraction analysis (XRD), UV–Vis spectroscopy, transmission electron microscopy (TEM), and photoluminescence (PL). The photocatalytic performances of the obtained materials were evaluated by the photodegradation under UV light irradiation of two different common pollutants: rhodamine B (RhB) and sodium dodecyl sulfate (SDS). The mechanism of the involved photocatalytic process was studied by the investigation of the main oxidants responsible of the photodegradation, using hole or radical scavengers. The antibacterial properties were investigated using Escherichia coli as a model organism. The eventual toxic effects of the prepared materials were studied on Artemia salina.