Computer-implemented methods of optimizing a process simulation model that predicts a result of a semiconductor device fabrication operation to process parameter values characterizing the semiconductor device fabrication operation are disclosed. The methods involve generating cost values using a computationally predicted result of the semiconductor device fabrication operation and a metrology result produced, at least in part, by performing the semiconductor device fabrication operation in a reaction chamber operating under a set of fixed process parameter values. The determination of the parameters of the process simulation model may employ pre-process profiles, via optimization of the resultant post-process profiles of the parameters against profile metrology results. Cost values for, e.g., optical scatterometry, scanning electron microscopy and transmission electron microscopy may be used to guide optimization.