This study discusses a quantitative fatigue evaluation of polymer–ceramic composites for dental restorations, i.e., commercial (Filtek Z550) and experimental Ex-nano (G), Ex-flow (G). Their evaluation is based on the following descriptors: mechanical strength, elastic modulus and strain work to fracture. Supposed to reflect factors of environmental degradation conditions, thermal fatigue was simulated with a special computer-controlled device performing algorithms of thermocycling. The specimens intended for the strength test underwent 104 hydro-thermal fatigue cycles. This procedure of thermocycling was preceded by aging, which meant immersing the specimens in artificial saliva at 37 °C for 30 days. The strength tests after aging only and after aging and thermocycles were performed in line with the three-point flexural strength (TFS) test, specified in ISO 4049, and the biaxial flexural strength (BFS) test, specifically piston-on-three-ball in accordance with ISO 6872. Based on the results, it can be stated that composites with higher volume content of inorganic particles after aging only show higher strength than materials with lower filler particle content. For example, the average flexural bending strength of the Ex-flow (G) composite was about 45% lower than the value obtained for the Ex-nano (G) material. The residual strength after thermocycles is significantly lower for the experimental composites, whereas a smaller decrease in strength is recorded for the commercial composites. Decreases in strength were about 4% (Filtek Z550), 43% (Ex-nano (G)), and 29% (Ex-flow (G)) for the BFS test; and about 17% (Filtek Z550), 55% (Ex-nano (G)), 60% (Ex-flow (G)) for the TFS test. The elastic modulus of the experimental composites after only aging is higher (about 42%) than that of the commercial composite, but the elastic modulus of the commercial composite increases significantly after thermocycling. A descriptor known as strain work to fracture turns out to be a good descriptor for evaluating the hydro-thermal fatigue of the tested polymer–ceramic composites.