Sorry, I didn't realize you were working with an existing experimental data set that you didn't create.
Regarding your situational examples; The level setting in the experiment and the associated noise that changes during the experiment creates the inference or design space. In your hypothetical, "the temperature variation is not well understood", if the temp is not well understood, study it! How confident would you be in results from a simulation that assumes some distribution and some amount of total variation?, Or "is thought to be random within a specific range (e.g. 35 - 45 C), and only the low, mid, high were tested from the DoE", I would suggest that if the low were 35º and the high was 45º and a third level at the center 40º then you have a fairly good understanding of that space. Realize, that a simulation is based on an algorithm (model) already known. Perhaps the model was created as a result of an experiment. The inference space of the experiment is still a restriction on the viability of the model. Can you hypothesize what might happen as you use your model to predict outside of the inference space? Of course, but you would be better served to actually run experiments over a wider inference space.
"All models are wrong, some are useful" G.E.P. Box