Ground transportation industry contributes to about 14% of the global CO2 emissions. Therefore, any effort in reducing global CO2 needs to include the design of cleaner and more efficient vehicles. Their design needs to be optimized for the real-world conditions. Using wind tunnels that can only reproduce idealized conditions does not always translate in real-world CO2 reduction and increased energy efficiency. Several recent studies found that very rarely can the real-world environment be represented by turbulence-free conditions in wind tunnels. The real-world conditions consist of both a transversal flow velocity component (which creates an oncoming yaw flow) as well as large-scale turbulent fluctuations, with length scales of up to many times the size of the vehicle. The study presented in this paper shows how the realistic wind affects the aerodynamics of the vehicle. The real-world aerodynamic drag of the vehicle is used in a system model tool to predict the changes in energy consumption and CO2 emissions under various duty cycles. The goal is to compare the on-road fuel economy considering realistic wind, in contrast to the standard drive cycle obtained with ideal flow conditions. Different wind characteristics or wind profiles, representing different geography or typical route conditions, were tested to assess their effects on the drive cycle. The use of real-world aerodynamics to predict a more realistic load curve could also impact the tuning of the vehicle sub-systems, like the transmission mappings, cooling module design, cooling flow sizing, heat exchanger properties, active grille shutter control map, etc. This work describes new techniques to design the vehicle including real-world aerodynamics, cooling module and other systems, in order to improve fuel economy for on-road driving.