Synergistic antimicrobial activity between natural, synthetic and nanoparticles have the potential to improve the microbiological safety of foods. The aim of this study was to evaluate the effectiveness of combined nisin 1000 IU/mL (N), lysozyme 500 U/mL (L), EDTA nanoparticles 5mM (E) or ZnO nanoparticles 12mM (Z) against 3 foodborne pathogens associated with packed minced beef during storage at 4 ˚C. The LNZ and LNEZ combinations showed effect against Escherichia coli O157:H7, while LE, NE, LZ, NZ, LNZ, and LNEZ were effective against Listeria monocytogenes. Moreover, LZ, NZ, LNZ, and LNEZ had the ability to inhibit Bacillus cereus. The compounds exhibiting the greatest antimicrobial activity were applied for the further challenge studies on minced beef. The LNZ and LNEZ were the most synergistic antimicrobial compounds and effectively inhibited the 3 foodborne pathogens, reducing microbial population between ~2 and 4 log CFU/cm2 in packed minced beef stored at 4˚C for 15 days. The results demonstrated that natural antimicrobials in combination with nanoparticles may effectively inhibit foodborne pathogens and enhance the safety of refrigerated meat products.