The growing demand for antibacterial materials, particularly for biomedical and packaging applications, has prompted significant interest in biodegradable alternatives to traditional plastics. Among these, poly(lactic acid) (PLA) is a biocompatible and biodegradable polymer that is increasingly being recognized as a promising matrix material for the development of functional nanocomposites. Notably, the incorporation of zinc oxide (ZnO) nanoparticles into PLA matrices enhances their antibacterial functionality, providing effective solutions against both Gram-positive and Gram-negative bacteria. However, challenges persist in manufacturing PLA/ZnO nanocomposites, including achieving uniform nanoparticle dispersion, ensuring interfacial compatibility, and addressing scalability issues for industrial applications. Moreover, ongoing scientific debates regarding the exact antibacterial mechanisms of ZnO, such as reactive oxygen species (ROS) generation, physical disruption of bacterial membranes, and zinc ion release, complicate the efforts to optimize these materials. This review summarizes the current state of research on PLA/ZnO nanocomposites, exploring both the manufacturing challenges and the scientific discussions regarding their antibacterial mechanisms. Consequently, by identifying unresolved questions and consolidating existing knowledge, this review provides valuable insights for researchers and engineers seeking to advance the development of effective antibacterial materials, ultimately contributing to solutions to global health and environmental challenges.