Hybrid sandwich structures are more and more widely used in many industries. This is mainly due to their good properties. One of the limitations regarding the use of sandwich structures is their difficult processing. Therefore, it seems reasonable to determine the influence of cutting parameters and machining configuration on the characteristic defect (phase) formed at the boundary of the materials forming a hybrid sandwich structure. This study investigates the effects of layer orientations during milling and machining parameters such as the cutting speed Vc, the feed fz and the cutting width ae. The study is conducted on a two-layer sandwich structure composed of two materials: 2024 aluminum alloy and epoxy-carbon composite with 60% of high-strength carbon fibers. A statistical analysis is performed using the Statistica program. The results show that the change in the cutting parameters has a greater impact on the formation of a defect on the surface of samples when the machining process starts on the side of the composite rather than the metal. The highest defect value is obtained for the milling from the composite layer when the process is performed with the following cutting parameters: Vc = 300 m/min, fz = 0.08 mm/tooth, ae = 5 mm.