Centrifugal compressor performance is affected by many parameters, optimization of which can lead to superior designs. Recognizing the most important parameters affecting performance helps to reduce the optimization process cost. Of the compressor components, the impeller plays the most important role in compressor performance, hence the design parameters affecting this component were considered. A turbocharger centrifugal compressor with vaneless diffuser was studied and the parameters investigated included meridional geometry, rotor blade angle distribution and start location of the main blades and splitters. The diffuser shape was captured as part of the meridional geometry. Applying a novel approach to the problem, full factorial analysis was used to investigate the most effective parameters. The Response Surface Method was then implemented to construct the surrogate models and to recognize the best points over a design space created as based on the Box-Behnken methodology. The results highlighted the factors that affected impeller performance the most. Using the Design of Experiment technique, the model which optimized both efficiency and pressure ratio simultaneously delivered a design with 3% and 11% improvement in each respectively in comparison to the initial impeller at the design point. Importantly, this was not at the expense of sacrificing range, of critical concern in compressor design.