The purpose of this in vitro study was to evaluate the effect of the non-thermal plasma (NTP) treatment on the wettability and surface roughness of different types of CAD/CAM materials as well as the shear bond strength (SBS) of adhesive resin cement to the treated surfaces. Three different materials, namely; resin nano ceramic, feldspathic ceramic and poly(methyl methacrylate) (PMMA)-based samples were treated with NTP for different time points to evaluate the effect of NTP treatment on the surface properties of CAD/CAM materials. Moreover, surfaces of CAD/CAM materials were visualised with scanning electron microscopy (SEM). A 90-second NTP treatment time was determined as the optimum time for the highest measured wettability, and thus, the 90-second NTP treated samples were used for the SBS test and evaluation of the failure types. Our results revealed the NTP treatment lowered the contact angles and increased the roughness of all tested materials. Moreover, The NTP treatment significantly enhanced the SBS of resin nano ceramic and feldspathic ceramic-based materials. NTP could be considered as a novel pre-treatment method to improve surface properties and the bonding performance of ceramic-based CAD/CAM materials.