This paper presents a simulation-driven approach to informing design decisions in resilient learning factories, focusing on the integration of what-if scenarios and simulation techniques to assess the impact of strategic decisions. Learning factories are complex systems, and decisions made during the design phase have a significant impact on characteristics for resilience. Practical implementations at the University of Twente (UT) demonstrate the application of the simulation-driven approach. Synthetic Environments (SEs) allow potential futures to be explored and visualised, helping stakeholders to understand the consequences of design-decisions. Additionally, a case study at UT using Discrete Event Simulation (DES) demonstrates that insights into the effects of decisions on the behaviour of the manufacturing system can be gained by simulating scenarios. The results highlight the value of simulations in guiding design decisions and provide conclusions in using flexibility as a strategic approach to develop resilient learning factories. This paper also discusses the potential for further integration of simulation techniques during the entire life cycle of the learning factory to continuously refine the design and promote resilience over time.