Spices are often sun-dried and may be severely contaminated by microorganisms from harvest to consumption. In this study, natural contamination by microflorae in 180 dry pepper samples: 60 Sichuan pepper, 60 white pepper, and 60 chili pepper samples in 22 districts of Sichuan Province, China, was investigated. Three samples with the highest bacterial counts were isothermally inactivated at 80 °C and 100 °C. We then examined the effect of water activity at 25 °C (aw,25°C) on iso-thermal inactivation efficacy in white pepper. Results showed severe natural microbial contamination in pepper samples, and as high as 50%–85% of the samples were off-specification. We hardly obtained <102 CFU/g in the piece heated at 80 °C or 100 °C for 80 min, and reducing the aw,25 °C values of two white pepper samples increased the D-values. We screened six surviving strains from dry pepper samples heated at 100 °C for 100 min, and whole-genome sequencing showed that they belonged to the genus Bacillus. Each strain had one virulence gene, including hasC, bslA, and flip, and a few antibiotic resistance genes (2–9). Conventional heat treatments cannot control microorganisms in peppers without compromising quality and may be accompanied by food safety risks.