The concept of Industry 4.0 represents an innovative vision of what will be the factory of the future. The principles of this new paradigm are based on interoperability and data exchange between dierent industrial equipment. In this context, Cyber- Physical Systems (CPSs) cover one of the main roles in this revolution. The combination of models and the integration of real data coming from the field allows to obtain the virtual copy of the real plant, also called Digital Twin. The entire factory can be seen as a set of CPSs and the resulting system is also called Cyber-Physical Production System (CPPS). This CPPS represents the Digital Twin of the factory with which it would be possible analyze the real factory. The interoperability between the real industrial equipment and the Digital Twin allows to make predictions concerning the quality of the products. More in details, these analyses are related to the variability of production quality, prediction of the maintenance cycle, the accurate estimation of energy consumption and other extra-functional properties of the system. Several tools [2] allow to model a production line, considering dierent aspects of the factory (i.e. geometrical properties, the information flows etc.) However, these simulators do not provide natively any solution for the design integration of CPSs, making impossible to have precise analysis concerning the real factory. Furthermore, for the best of our knowledge, there are no solution regarding a clear integration of data coming from real equipment into CPS models that composes the entire production line. In this context, the goal of this thesis aims to define an unified methodology to design and simulate the Digital Twin of a plant, integrating data coming from real equipment. In detail, the presented methodologies focus mainly on: integration of heterogeneous models in production line simulators; Integration of heterogeneous models with ad-hoc simulation strategies; Multi-level simulation approach of CPS and integration of real data coming from sensors into models. All the presented contributions produce an environment that allows to perform simulation of the plant based not only on synthetic data, but also on real data coming from equipments
