Myositis tropicans or pyomyositis is a muscle inflammation resulting from a bacterial infection of skeletal muscle (commonly caused by Staphylococcus aureus) that usually leads to hematogenous muscle seeding. The present study was designed to estimate the role of ZnO-NPs and a physiotherapeutic program in the management of induced biceps femoris atrophy in rats through histological, biochemical, and radiological examinations at different time intervals. At the beginning, several bacterial strains were evaluated through a proteolytic enzyme activity assay and the highest activity was recorded with the Staphylococcus aureus strain. ZnO-NPs were synthesized with the arc discharge method with an average size of 19.4 nm. The antibacterial activity of ZnO-NPs was investigated and it was revealed that the prepared ZnO-NPs showed a minimum inhibitory concentration of 8 µg/mL against the tested bacterium. The cytotoxicity of the prepared ZnO-NPs was tested in C2C12 myoblast cells, and it was elaborated that CC50 was 344.16 µg/mL. Biceps femoris pyomyositis was induced with a potent strain (Staphylococcus aureus); then, a physiotherapeutic program combined with the prepared ZnO-NPs treatment protocol was applied and evaluated. The combined program claimed antibacterial properties, preventing muscle atrophy, and resulted in the most comparable value of muscle mass.