Working at and above head height with a power tool represents a common activity in craft and assembly applications. To assist and protect the user from overload and injuries in these situations, the development and use of application-specific support systems, such as exoskeletons and power tools, have greatly increased in recent years. Thus, the integration of aspects of the user-centered product development of support systems in the early phases of product development process has high potentials. A common approach to integrate the user early in the product development process is the use of musculoskeletal human models, which allow the evaluation of effects on the human body. This could also be applicable in the mentioned use case to enable the evaluation of the interactions for the user. Therefore, a co-simulation model for virtual modelling and simulating human–machine interactions is presented. The co-simulation model is made up of a musculoskeletal human model and the models of the technical systems (exoskeleton and power tool). By applying the co-simulation model, the impact of technical systems on the human body can be taken into account to derive design alternatives for the technical system due to the requirements of the user. The paper describes the design of the co-simulation model and particularly, the interaction of the submodels. The evaluation of the co-simulation model is carried out with the help of a subject study for the selected use case working at and above head height. The results show plausible results for the muscle loads considering the support by an exoskeleton. Furthermore, the comparison of simulated results to measured muscle activations via surface electromyography shows a good agreement. Thus, the co-simulation model passes the test for functionality and seems to be applicable for the derivation of design alternatives of technical systems regarding the user needs. In future, the co-simulation model will be further validated with a higher number of subjects and to implement design alterations in the technical systems.