In modern manufacturing systems, which are often referred to as Industry 5.0, increased importance is given to people and environmental protection where the use of natural fiber-reinforced composite polymers comes into place. In this paper, we studied hybrid epoxy composites comprising natural bamboo and glass fibers and investigated their mechanical and thermal performance in view of Industry 5.0. Ready-to-use materials such as bamboo which is cheap, readily available, and mechanically strong are encouraging reinforcement alternatives. The influence of various orientations of glass fiber that is 0, 30, 45 and 60° on the properties of bamboo–epoxy composites in terms of compressive strength, impact resistance, hardness, and thermal properties has been carried out. It was found that a 45° direction provides the best hardness and compression strength vice versa, whereas impact strength was optimal at a 0° direction. Further, challenges to the integration of Industry 5.0 such as the use of a digital twin for fiber orientation optimization, use of smart sensors for increasing thermal stability, and analytics and IoT for real-time optimization are elaborated. This chapter helps in an overall understanding of mechanical performance, thermal performance, and the relations of the two toward sustainability of the application of nonfiber-reinforced polymers composites in advanced manufacturing systems. The comparative analysis of advantages and disadvantages of changes from a linear model with high levels of ecologically dangerous production and wastes toward a much more dynamic Industry 5.0 is illustrated as well.