During development of new vehicles, CAE driven optimizations are helpful in achieving the optimal designs. In the early phase of vehicle development there is an opportunity to explore shape changes, gage reduction or alternative materials as enablers to reduce weight. However, in later phases of vehicle development the window of opportunity closes on most of the enablers discussed above. The paper discusses a simplified methodology for reducing the weight in design cycle for truck frames using parametric Design of Experiments (DOE). In body-on-frame vehicles, reducing the weight of the frame in the design cycle without down gaging involves introducing lightening holes or cutouts while still maintaining the fatigue life. It is also known that the lightening holes might cause stress risers and be detrimental to the fatigue life of the component. Thus the ability to identify cutout locations while maintaining the durability performance becomes very critical. This paper describes a method of effectively locating these lightening holes on the truck frame, thereby reducing the weight of the vehicle while preserving the durability performance.The process to incorporate these lightening holes is a multi-step approach beginning with a stress envelope creation. The load paths for each component are identified based on the stress envelops generated in the fatigue code using a complete set of proving ground loading events. A subsequent step includes tuning those lightening holes to meet the durability, strength and stiffness requirements via the automated process of resizing the lightening holes to their optimal sizes. The final verification is carried out with the regular analysis procedure to verify the lightening holes effect on the durability performance of the structure.