High-moisture extrusion cooking (HMEC) is an efficient method for converting proteins and polysaccharides into fibrous structure that is used in the industrial production of meat analogs. The purpose of this review is to systematically evaluate current knowledge regarding the modification of protein structure including denaturation and reassembly upon extrusion processing and to correlate this understanding to the structure of the final products. Although there is no consensus on the relative importance of a certain type of bond on extrudates' structure, literature suggests that, regardless of moisture level, these linkages and interactions give rise to distinctive hierarchical order. Both noncovalent and disulfide bonds contribute to the extrudates' fibrous structure. At high water levels, hydrogen and disulfide bonds play a dominant role in extrudates' texture. The process parameters including cooking temperature, screw speed, and moisture content have significant albeit different levels of impact on the texturization process. Their correlation with the ingredients' physiochemical properties provides a greater insight into the process-structure-function relationship of meat analogs. The tendency of protein and polysaccharide blends to phase separate rather than produce a homogeneous mix is a particularly important aspect that leads to the formation of fibrous layers when extruded. This review shows that systematic studies are required to measure and explain synergistic and competitive interactions between proteins and other ingredients such as carbohydrates with a focus on their incompatibility. The wide range of plant protein source can be utilized in the HMEC process to produce texturized products, including meat analogs.