Real-time simulation and digital twin (DT) as a part of Industry 4.0 are becoming increasingly relevant, especially when considering production cycles. Most issues with production cycles arise from having a demand for customized production orders, while having nonmodular production lines with a medium-to-high complexity in the decision-making process. All these conditions lead to a possibility of unpredictable consequences. Being able to predict behavior and possible failure scenarios before the production starts has proven to save both costs and time. With an introduction of a new ISO standard which is solely focused on DT creation and sets a starting point for future research, researchers are finally able to focus on creating DT prototypes built for specific scenarios while maintaining the core concepts. This paper focuses on proposing strategies for DT and real-time simulation integration into production cycles, based on the new standards, which can be generalized and applied on a multitude of different systems with minimal changes. The proposed solutions offer different levels of human interaction with the Human–Machine Interfaces used in Cyber–Physical Systems created as a part of DT. Applicability of the solution has been verified based on the results of experiments carried out on the WITNESS Horizon simulation platform with utilization of the custom Order Manipulation Interface (OMI) application.