The design strategy of a food process must be aimed to provide food safety while retaining optimal organoleptic and nutritional characteristics and, possibly, to optimize the energy consumption. As a matter of fact, it represents a challenge in food process engineering. In this framework, it is essential to determine the interactions among transport phenomena (mass, heat, and momentum) and any other relevant physics for further optimal design and for driving possible innovation. In other technological sectors (like automotive or aerospace industries), virtualization and mathematical modeling are standard methods used for optimal design, while in food process engineering the contribution of such tools has not been fully exploited. Since virtualization represents a new and sophisticated strategic tool to design and to innovate a process, the objective of this review was to introduce virtualization and mathematical modeling in the food processing industry. For this purpose, motivation and needs for virtualization in food processing were focused, mathematical modeling background and various approaches for modeling were introduced, and solution methods and required initial–boundary conditions with thermal-physical properties were outlined. Also complexity, computational cost, and model validation techniques were critically discussed. Virtualization and mathematical modeling dominate the major requirements to design, optimize, and innovate food processing with their vast opportunities and potentials and they will become a cornerstone of utmost importance to food engineering domain