In the last years, the increase of data availability together with enhanced resource flexibility shed light on the possibility to develop planning and control methods with real-time inputs. Literature is rich of approaches to simulate, to quickly evaluate system performances, and to take decisions based on optimization criteria. Further, simulation has been identified as one of the pillars for the Industry 4.0 revolution. However, the lack of a generally recognized approach and methodology to deal with real-time decision-making through simulation is evident. Simulation approaches can and should play a central role in industry for the years to come. This position paper analyses the current research context with a brief state of the art on existing approaches, includes considerations about the issues for implementing Real-Time Simulation (RTS) concepts and their current state of development. Finally, it outlines research directions for the simulation community.