Using conventional drilling for bolted joints in carbon fiber reinforced polymer (CFRP) composites leads to secondary damage and defects that compromise their structural strength and integrity. Development of new solutions and optimization of drilling process methods and parameters are needed to minimize damage in the proximity of the drilling site and maximize hole quality. Hence, the non-destructive detection and quantification of hole damage become important tasks in the design and optimization of the drilling process. Furthermore, the development of process models for drilling needs non-destructive metrics that characterize damage and thermomechanical signatures that result from the process. This work presents results gathered from experimental studies of drilling techniques optimization in CFRP panels in terms of multiple non-destructive evaluation (NDE) methods. First, the combinations of drilling process parameters and drill bits engineered for the panels are presented. Then, hole quality and hole damage parameters are discussed in terms of temperature–time histories collected in situ with infrared thermography, through hole surface roughness measurements from profilometry, and internal damage characterization from ultrasonic C-scan testing. Particularly for the latter, ultrasonic scattering analyses are performed to characterize internal damage accurately, while maximizing detection throughput. The preliminary results can be used to guide the selection of optimal drilling process parameters and bit design, while also providing fundamental knowledge on hole damage initiation for the development of process-dependent failure prediction models. Finally, challenges and opportunities for using multiple NDE techniques for accurate drill process monitoring are discussed.