Effective control or inactivation of foodborne pathogens is an important process to ensure product microbiological safety and consumer health. To address food safety issues and extend product shelf-life to obtain high-quality or value-added products, the food industry is adopting emerging thermal and non-thermal technologies. The inactivation mechanism of these technologies is mainly achieved by destroying the cellular morphology and molecular structure required by microorganisms to maintain normal physiological functions. Therefore, clarifying the mechanism of action is important for the process optimization and application of these technologies. This review provides an overview of the potential risks of several common foodborne pathogens, highlights the application of several typical new technologies (ohmic heating, microwave heating, pulsed electric field, cold plasma, etc.), illustrates the inactivation mechanisms of these technologies at the cellular and molecular levels in detail, and indicates the current problems and future challenges of these novel technologies in food sterilization processing. The conclusions suggest that a systematic analysis of thermal and non-thermal effects and their inactivation mechanisms remains a challenge. Although different foodborne pathogens share similarities in cellular structure and defense and stress mechanisms, they differ in their resistance to the physical environment. It is difficult to identify specific targets for inactivating pathogens during processing.