Thermal treatments are essential to abate the microbial load in food matrices and ensure food safety. Heat exchangers (HEs) are commonly adopted for the pasteurization of liquid foods, thanks to their simple structure and ease of use. In particular, tubular HEs are often employed with viscous fluids and products containing fibres and pieces. The aim of pasteurization is to ensure that every point of the product reaches and maintains the target temperature for an adequate amount of time. To this end, it is essential to guarantee uniformity and prevent portions of fluid from reaching an insufficient temperature, and others from being overheated. To evaluate the thermal treatment inside a tube-in-tube HE, computational fluid dynamics (CFD) was used to simulate a pilot plant. Three different fluids with shear-thinning temperature-dependent non-Newtonian behaviour were evaluated. A CFD simulation campaign was carried out reproducing, for each juice, the thermal treatment under different operating conditions. Then, the results were analysed with statistical techniques to evaluate the impact of each operating parameter on the treatment, highlighting how high viscosity greatly impacts the thermal treatment, resulting in lower average temperature and temperature uniformity, while causing an increase in the pressure drop. The results of the simulation campaign were also used to generate a reduced order model (ROM) of the device, that could be exploited to estimate the outcomes of a treatment both as averaged values on a section or at a specific point like “virtual sensors”. The ROM could be also adopted to design and evaluate alternative treatments by performing numerical optimization based on given objectives and constraints. Finally, as the ROM can be implemented in real-time, it could be used to monitor and control the functioning of food plants, detecting deviations from the expected conditions and possible failure conditions.