In the era of the fourth industrial revolution, human has still a central role. Manufacturing industries have to deal with human sustainability in order to guarantee workers’ health and well-being. Several studies have proved the importance of ergonomics in workplace design and the benefits related to the adoption of the human-centered approach. The enabling technologies of Industry 4.0 are changing the role of the operator and can support him from a physical and cognitive point of view. On the other hand, companies are increasingly implementing lean philosophies, such as World Class Manufacturing, to maintain their competitiveness by reducing wastes and costs. However, the need arises for a comprehensive methodology to support the design of manufacturing equipment considering human factors by integrating Industry 4.0 technologies and World Class Manufacturing elements. It aims at improving both ergonomic and efficiency aspects of the workstation. The proposed methodology allows identifying and in-depth analyzing the problem, thus finding and implementing a solution that complies with all the requirements and constraints defined. Each step of the methodology can be strengthened by Industry 4.0 technologies. The methodology has been experimented in a real case study with a global company of agriculture and industrial vehicles, leading to the design and implementation of a new equipment. Relevant benefits in terms of ergonomics, efficiency, and process standardization have been achieved.