In this work, the modification process of poly(lactic acid) (PLA) with metal-based nanoparticle (NPs) additives (Ag, ZnO, TiO2) at different loading (0.5, 1.0, and 2.5 wt%) and by melt-mix extrusion method followed by film formation as one of the advantageous techniques for industrial application have been investigated. PLA nanoparticle composite films (PLA-NPs) of PLA-Ag, PLA-ZnO, PLA-TiO2 were fabricated, allowing convenient dispersion of NPs within the PLA matrix to further pursue the challenge of investigating the surface properties of PLA-NPs reinforced plastics (as films) for the final functional properties, such as antimicrobial activity and surface mechanical properties. The main objective was to clarify how the addition of NPs to the PLA during the melt extrusion process affects the chemistry, morphology, and wettability of the surface and its further influence on the antibacterial efficiency and mechanical properties of the PLA-NPs. Therefore, the effect of Ag, ZnO, and TiO2 NPs incorporation on the morphology (SEM), elemental mapping analysis (SEM-EDX), roughness, surface free energy (SFE) of PLA-NPs measured by goniometry and calculated by OWRK (Owens, Wendt, Rabel, and Kaelble) model was evaluated and correlated with the final functional properties such as antimicrobial activity and surface mechanical properties. The developed PLA-metal-based nanocomposites, with improved mechanical and antimicrobial surface properties, could be used as sustainable and biodegradable materials, offering desirable multifunctionalities not only for food packaging but also for cosmetics and hygiene products, as well as for broader plastic products where antimicrobial activity is desirable.