Developing new competitive approaches to the physical and virtual world integration with cyber-physical systems (CPS) is one of the European Union research priorities. CPS change the way people interface with systems, similarly to the way in which the Internet has transformed the way people interface with information. The two-hemisphere model-driven approach (2HMD) assumes modelling and use of procedural and conceptual knowledge on an equal interrelated basis. This differentiates the approach from pure procedural, pure conceptual, and object-oriented approaches. 2HMD approach may be applied in the context of modelling of a particular business domain as well as in the context of modelling the knowledge about the domain. CPS are heterogeneous systems which require a multi-disciplinary approach for their modelling. Modelling of cyber-physical systems by the 2HMD approach is a novel aspect of its application and gives an opportunity to transparently compose system components to be provided and components actually provided, thus to identify and fill the gap between desirable and actual system content. In this chapter the application of 2HMD approach to modelling of CPS is demonstrated through a case study.