The hard-to-cut materials and composites have been progressively replacing the aluminium usually applied in the complex aircraft structural assemblies. The titanium alloys and stainless steels for example are able to maintain their mechanical properties at high temperatures. Therefore, these three material together form interfaces in aircraft spars, ribs, skins and other structural parts. The assembly of these structures demands several manufacturing stages, including the drilling operation. When the materials are stacked on, it is hard to achieve surface finishing and dimensional accuracy quality requirements, due to the different behaviors of each metal, and due to the interference of the lower layers' chips in the upper layers. The scientific project here proposed, executed an experimental investigation on the drilling process of the aluminium, titanium and stainless steel metal plates. They were configured individually and as multi-layered metal structure. Experimental runs combined two cutting speeds, two cutting feeds and four different commercial drills using the design of experiments (DoE) approach. Further statistical complement with analysis of variance (ANOVA) determined the contribution of the factors on the hole diameter, circularity and cylindricity. Base on the results, it was possible to affirm that the tool geometry is capable to influence responses as diameter, cylindricity and circularity with more than 90% of confidence level. Roughness and burr also were investigated. The holes' scanned surface of the metals drilled separately presented good aspect, but in multi-stack it was evidenced height Ra and Rmax suggesting an additional process to ream the holes. The indicators thrust force and chips formation complemented the results.