Pathogens in low water activity foods are an important emerging food safety concern due to notable survival and thermotolerance. Limited but growing data are publicly available to compare the thermotolerance of Listeria monocytogenes, Salmonella spp., and Enterococcus faecium NRRL B-2354 (a Salmonella surrogate). The aims of this study were to determine and assess bacterial thermal inactivation rates of two pathogens and a well-established surrogate across three different low-moisture food matrices containing different levels of fat using a dry inoculation method. Three low-moisture foods (0.11 aw, 45% fat peanut butter; 0.20 aw, 27% fat powder infant formula; and 0.45 aw, < 2% fat wheat flour) were inoculated at room temperature (24.8 °C) with a dry inoculum containing either E. faecium, a Salmonella spp. cocktail, or a L. monocytogenes cocktail. Uniform bagged samples across the 9 treatments were sandwiched in copper plates and heat-treated via immersion in a hot water bath during isothermal treatments ranging from 60 °C to 90 °C. The tests were conducted in triplicate. Bacterial survival was detected via direct plating on tryptic soy agar with 0.6% yeast extract. In peanut butter and most of the powder infant formula treatments, Salmonella spp. had significantly higher D-values than L. monocytogenes using comparable temperatures (p < 0.05). However, D65°C- and D75°C-values between Salmonella spp. and L. monocytogenes in wheat flour and D85°C-values in powder infant formula were undifferentiated. E. faecium had significantly higher D-values than L. monocytogenes and Salmonella spp. in each food matrix (p < 0.05). The singular exception was observed with D85°C-values between Salmonella spp. and E. faecium in peanut butter which were not statistically different. The observed matrix effect on thermotolerance for each of the bacteria was reported in descending order as powder infant formula > peanut butter > wheat flour for the vast majority of the comparable D-values. While Salmonella is the primary pathogen of concern in low-moisture foods due to survival and outbreaks, these results indicate L. monocytogenes can exhibit similar thermotolerances in low-water activity food matrices including peanut butter and powder infant formula.