This study investigated the isolated effect of modified atmosphere packaging (MAP; 50% CO2 and 50% N2) and ultraviolet radiation (UV; 0.30 J/cm2) as well as their combined (MAP/UV) effect on reduction of Salmonella typhimurium and Escherichia coli O157:H7, biogenic amines (BA), and on shelf life of tilapia fillets stored at 4 ± 1 °C for 10 days. UV samples had the highest reduction of S. typhimurium (1.13 log colony forming units/g; CFU/g) and E. coli O157:H7 (0.70 log CFU/g). MAP and MAP/UV reduced the growth of S. typhimurium in 0.50 log CFU/g and did not affect the growth of E. coli O157:H7. UV, MAP, and MAP/UV increased lag phase and/or generation time of all evaluated bacterial groups, decreased pH values, ammonia formation, texture changes, and, in general, the BA formation throughout storage period, and, therefore, UV, MAP, and MAP/UV extended the shelf life for two, three, and at least five days, respectively. MAP/UV, MAP, and UV decreased redness, MAP/UV and MAP increased yellowness and lipid oxidation, while UV did not affect it. MAP/UV demonstrated promising results for shelf life extension; however, different gas ratios in combination with other ultraviolet radiation type C (UV-C) doses should be investigated to reach the highest microbiological safety and maintenance of the overall quality of tilapia fillets.