Interventions against microbial contamination and cross-contamination are of great importance in areas that affect human health and life, including food processing, food handling, food service, and healthcare environments. As negative consumer reactions against the addition of chemical preservatives to foods, and concerns regarding the development of resistance to disinfectants in food processing and healthcare environments have increased, microbial intervention strategies using alternative nonthermal and physicochemical methods have been increasingly developed and adopted. Nonthermal technologies are mainly reliant on physical processes to achieve microbial reduction. They include, but are not limited to light-based electromagnetic radiation, high hydrostatic pressure, pulse electric fields, irradiation, and cold plasma. Another increasingly popular direction in alleviation of microbial contamination and cross-contamination is to use physicochemical approaches to develop materials with antifouling properties that prevent bacteria attachment to contact surfaces. In this work, the effect of both nonthermal light treatments on microbial inactivation and physicochemical nanoengineering on prevention of bacteria attachment on food contact surfaces were investigated. For both approaches, the factors affecting the antimicrobial efficacy were discussed, and both experimental and numerical strategies were used to explore strategies for improving their effectiveness. Light-based technologies are recognized as strong alternatives for the existing chemical cleaning systems on material surfaces as they leave no residues and have a broad spectrum of bactericidal efficacy. However, conventional ultraviolet (UV) mercury lamps have limitations including inactivation variability, low energy efficiency, and detrimental effects on mammalian cells. Chapter One to Three in this thesis present a quantitative assessment of the potential of various light-based technologies, as well as approaches to overcome the limitations of UV mercury lamps, including: 1) constructing an all-directional isotropic light distribution unit to maximize UV treatment efficacy, 2) adopting numerical ray tracing simulation to improve treatment predictability and control, 3) assessing the disinfection performance of different wavelengths (i.e., 405 nm visible light and 222 nm far-UV-C light) and varying light sources (i.e., LEDs and excimer lamps) in inactivation of both planktonic and biofilm-bound foodborne pathogens, and 4) designing a hurdle treatment using multiple wavelengths with different inactivation mechanisms to achieve synergistic disinfection effectiveness. In Chapter Four, an effective antifouling material was developed to prevent bacteria attachment and biofilm formation on abiotic food contact surfaces by using a physicochemical nanoengineering method. The effects of various surface properties were decoupled using the orthogonal nanoengineering (ONE) method, which improved the overall antifouling performance. Nanotopography was controlled by manufacturing anodic aluminum oxide (AAO) surfaces with cylindrical nanopores of various pore sizes, and surface chemistry was tuned by depositing zwitterionic polymer coating on the AAO surfaces. Quantitative assessments on the antifouling performance of these nanoengineered surfaces were conducted, and the experimental results confirmed improved bacterial attachment prevention and biofilm inhibition effects. Overall, this work expanded the current knowledge about nonthermal and physicochemical approaches for combating microbial contamination in different environmental conditions, and provided critical insights for food processors to implement these technologies in processing applications to improve food safety.