Simulation approaches have long been used in the context of supply-chain management (SCM). Unlike the conventional approach which models the different stages of SC as a single simulation, a distributed supply-chain simulation (DSCS) enables coordinated execution of existing models through use of distributed simulation middleware. The new era of Industry 4.0 has created the “smart factory” of cyber-physical systems which controls the route of products’ assembly line for customised configuration. The collaboration of all supply-chain players in this process is essential for the tracking of a product from suppliers to customers. Therefore, it becomes necessary to examine the role of distributed simulation in designing, experimenting and prototyping the implementation of the large number of highly interconnected components of Industry 4.0 and overcome computational and information disclosure problems amongst supply chain echelons. In this chapter, we present an overview and discuss the motivation for using DSCS, the modelling techniques, the distributed computing technologies and middleware, its advantages, as also limitations and trade-offs. The aim is to inform the organizational stakeholders, simulation researchers, practitioners, distributed systems’ programmers and software vendors, as to the state of the art in DSCS which is fundamental in the complex interconnected and stochastic environment of Industry 4.0.