This paper will discuss the process of drilling large diameter holes within high quality requirements using a Robot positioning concept. This Robot end-effector system provides flexibility to handle different aircraft sections due to its Robot arm design. The material configuration that will be discussed in this paper is a mixed material stack of CFRP and Aluminum. The diameter range is from 7.9 mm to 15.9mm. This paper will focus on the largest diameter (Ø15.9mm). It addresses the process forces to be handled and the solutions. This paper will take an integrated look at the whole process including machine, spindle, cutting tool design and process conditions. Only this integrated view to all process related items enables running an innovative and effective process.The maximum stack size of 40 mm is another condition that requires a specific process to control the chip size to avoid an impact to the material. Here different concepts have been taken under consideration. The paper will show an overview addressing these interesting concepts.