In this study, the design and practical implementation of a novel, scalable plug-flow pilot plant for hydrothermal liquefaction of organic feedstock is presented. The overall discussion comprises the system’s design, process modelling, and simulation, as well as results for an experimental validation of the proposed design with a focus on fluid dynamics and heat transfer. The design criteria take into account the scalability of the plug-flow processing system, optimized non-isothermal flow conditions of highly viscous liquids in a tubular system at harsh process conditions, specifically high pressure and medium temperatures, and overall maintenance suitability. A novel forced flow oscillation system as well as unique heat exchange design to reduce the energy consumption during system operation, maximize local flow mixing, and minimize plugging are proposed and experimentally tested. To achieve a better understanding and optimization of Hydrothermal Liquefaction (HTL) (and other) processing systems, a mathematical model of heat transfer coupled with non-isothermal fluid flow was also developed and implemented.