Consumption of plant-based meat analogues offers a way to reduce the environmental footprint of the human diet. High-moisture extrusion cooking (HMEC) and shear cell processing both rely on thermo-mechanical treatment of proteins to product fibrous meat-like products. However, the mechanisms underlying these processes are not well understood. In this review we discuss the effect of thermo-mechanical processing on the physicochemical properties and phase behavior of proteins and protein mixtures. The HMEC and shear cell processes are comparable in their basic unit operations, which are (1) mixing and hydration, (2) thermo-mechanical treatment, and (3) cooling. An often overlooked part of the extruder that could be crucial to fibrillation is the so-called breaker plate, which is situated between the barrel and die sections. We found a lack of consensus on the effect of heat on protein-protein interactions, and that the experimental tools to study protein-protein interactions are limited. The different mechanisms for structure formation proposed in literature all consider the deformation and alignment of the melt. However, the mechanisms differ in their underlying assumptions. Further investigation using novel and dedicated tools is required to fully understand these thermo-mechanical processes.