Engineers face significant challenges in developing cyber-physical systems (CPS) due to their heterogeneous nature, i.e. the need for knowledge and skills from a wide range of academic and industrial disciplines, the integration of the artifacts of these disciplines and fields, and the difficulty of maintaining such heterogeneous artifacts should be taken into account. The development of CPS mostly needs a unified methodology that permits efficient raise of the abstraction level to overcome issues of heterogeneity induced by the multidisciplinary nature of the system. Model-driven engineering (MDE) is believed to be an alternative solution to overcome the challenges faced while developing CPS. This paper presents a systematic mapping study on using the MDE paradigm in CPS development and management. 140 research papers published during the period 2010–2018 are evaluated. The study mainly enables to find out the followed approaches when applying MDE for CPS, addressed CPS challenges, application domains and presented case studies. Results showed that the number of publications in this field is continuously increasing in recent years. Results also showed that metamodeling and model-based approaches are mostly adopted by the researchers affiliated to Europe, while DSL-based approach is adopted mostly by USA affiliated researchers. Only 45% of the studies consider a specific CPS application domain in which Smart Manufacturing is the most addressed domain followed by Critical Infrastructure, Health Care and Medicine. Moreover, the majority of the studies present case studies as the main evaluation method for the proposed MDE solutions. Conducting empirical evaluations is mostly missing. The results also revealed that various CPS challenges are addressed, and the most addressed ones are the complexity and interoperability aspects of CPS. Reporting on what previous researches have accomplished, as well as current research efforts and open challenges related to this field can guide researchers and developers in their further work on CPS design and implementation.