The microbial safety and quality of Vacuum Packed (VP) hot-processed filleted smoke flavored Nile Tilapia (Oreochromis niloticus) in different moisture content at various time and temperature were examined during eight (8) weeks at room (320C) and refrigerated (40C) temperature. Moisture content was determined according to the method of AOAC (2002a). In this study, no significant differences (P > 0.05) were found between any of the samples of the color, aroma and saltiness attributes while flavor and texture and aroma were significantly different (P<0.05). The sensory evaluation panel also indicated that the most favorable smoked tilapia was the product stored at refrigerated temperature (40C) with 20% moisture content and the most acceptable products for panelists. The yeast and molds using the parameters of Yeast & Molds in food associated with the vacuum-packed smoked flavored Nile Tilapia stored room and refrigerated temperature, the yeast and mold count was less than 150 cfu/g. Thus, proper packaging, storage and hygienic processing improves the quality and safety of smoked fish. Level of proximate minerals content obtained in this study is within the standard provided by FAO (2007) for both STAP AND STVP. Hence, packaging is one of the most important technologies to be considered in any fish processed products.