A full calibration exercise of a diesel engine air path can take months to complete (depending on the number of variables). Model-based calibration approach can speed up the calibration process significantly. This paper discusses the overall calibration process of the air-path of the Cat® C7.1 engine using statistical machine learning tool. The standard Cat® C7.1 engine's twin-stage turbocharger was replaced by a VTG (Variable Turbine Geometry) as part of an evaluation of a novel air system. The changes made to the air-path system required a recalculation of the air path's boost set point and desired EGR set point maps. Statistical learning processes provided a firm basis to model and optimize the air path set point maps and allowed a healthy balance to be struck between the resources required for the exercise and the resulting data quality.