Cyber-physical systems (CPS) are increasingly integral to critical sectors such as healthcare, transportation, and manufacturing. Technological advancements have enhanced the capabilities of CPS, but their design often overlooks human factors, encompassing ergonomic, cognitive, and psychological elements. This oversight can lead to user errors, decreased efficiency, and safety risks. This chapter emphasizes the importance of integrating human factors into the CPS design. It explores the roles of cognitive, psychological, and physical elements in human–machine interaction, identifies challenges in considering human factors, and provides design principles centered on user-centered design, ergonomics, intuitive interfaces, human-in-the-loop systems, adaptive systems, real-time feedback, and multimodal interaction. Furthermore, it discusses future directions, including the integration of AI and machine learning to predict human responses, ethical and societal considerations, regulatory frameworks, and the necessity of interdisciplinary collaboration. Highlighting these aspects, the paper aims to bridge the gap between human capabilities and advanced CPS functionalities, promoting systems that are more effective, trustworthy, and accessible.