The challenge of high-mix low-volume production has reshaped manufacturing systems causing increased complexity in processes and growing sensitivity to the mix and temporal distribution of demand. Efficient evaluation and experimenting for decision support in such an environment is of key importance, however it is also extremely difficult as the complex interrelation between the affecting factors and the size of the input domain would require a large number of experiments to get reliable results. The paper introduces a method based on advanced data analysis for defining typical input scenarios, aiming to reduce the computational complexity of Discrete Event Simulation (DES) analysis. The presented approach was tested in a real-life combined (manufacturing and assembly) production line and the results showed that using scenarios for representing the typical input allowed reducing significantly the number of experiments required to execute sensitivity analysis of the structural (e.g. buffer size or workforce) and the operational (i.e. sequencing) parameters.