Sustainability, as one of three hallmark features of Industry 5.0, has attracted significant attention in manufacturing research and has become a significant driver of the development of innovative technologies and management concepts. With the fast development of human-centric smart manufacturing, a need arises to consider how this will affect the sustainability in terms of economic, social and ecological goals of manufacturing companies. What will the implications of human-centric smart manufacturing be on the decision-making of manufacturing activities, and how to integrate these sustainability goals into the human-centric instead of system-centric decision process? This chapter aims to answer these questions by synthesizing the diverse literature regarding human-centric smart manufacturing and sustainable manufacturing, and conceptualizing a reference framework in the perspective of manufacturing system engineering for sustainability performance evaluation and improvement. Finally, the research directions and challenges for Human-centric sustainable manufacturing are presented to provide a support to researchers and engineers willing to develop a human-centric sustainable and smart production system.