Composite material parts are typically laid out in near-net-shape, i.e., very close to the finished product configuration. However, further machining processes are often required to meet dimensional and tolerance requirements. Drilling, edge trimming and slotting are the main cutting processes employed for carbon fiber-reinforced plastic (CFRP) composite materials. In particular, drilling stands out as the most widespread machining process of CFRP composite parts, chiefly in the aerospace industrial sector, due to the extensive use of mechanical joints, such as rivets, rather than welded or bonded joints. However, CFRP drilling is markedly challenging: due to CFRP abrasiveness, inhomogeneity and anisotropic properties, tool wear rates are inherently high leading to superior cutting forces and detrimental effects on workpiece surface quality and material integrity. Damage such as delamination, cracks or matrix thermal degradation is often observed as the result of uncontrolled tool wear or improper machining conditions. Sensor monitoring of drilling operations is, therefore, highly desirable for process conditions’ optimization and tool life maximization. The development of this kind of automated control technologies for process and tool state evaluation can notably contribute to the reduction of scraps and tool costs as well as to the improvement of process productivity in the drilling of CFRP composite material parts. In this paper, multi-sensor process monitoring based on thrust force and torque signal detection and analysis was applied during drilling of CFRP/CFRP laminate stacks for the assembly of aircraft fuselage panels with the scope to evaluate the tool wear state. Different signal-processing methods were utilised to extract diverse types of features from the detected sensor signals. A machine-learning approach based on an artificial neural network (ANN) was implemented to make smart decisions on the timely execution of tool change, which is highly functional for CFRP drilling process automation.