A variable valvetrain gives possibility to apply advanced combustion process strategies such as the Miller cycle. As well-known, applying Miller timing is an effective way to reduce fuel consumption and NOx emissions for diesel engines. This becomes more and more inevitable with the intended future NOx emission limit of 0.02 g/bhp-hr and GHG limits for on-road HD CI engines. Previous studies of the authors have shown that the improvement potential highly depends on the achievable cylinder charge level. Increasing this (through additional increase in boost pressure) resulted in a significant decrease in ISFC as well as in an improved NOx-PM trade off. However, in these considerations the pressure difference of the charge air and the exhaust back pressure was kept on the same level. The paper to present investigates the improvement potentials for on-road HD CI engines with a whole system approach that means using a one dimensional six cylinder simulation model and taking a two stage turbocharger group into account. The air path model validated beforehand is based on a state-of-the-art series production engine, the combustion process and the emissions are directly taken over from measurements on a single cylinder test engine. The first part of the investigations shows the application of Miller timing on HD diesel engines, where charge air pressure increase was achieved through modified waste gate control and presents the change in fuel consumption as well as pollutant emissions. The second part focuses on an optimized strategy with scaled turbocharger size to maximize the improvements. The TC-scaling was based on geometrical similarities.