This in vitro study aimed to assess the influence of different concentrations and durations of hydrofluoric acid (HF) and Monobond Etch & Prime (MEP) etching on the surface roughness (Ra) of different CAD/CAM materials and on the shear bond strength (SBS) of a self-adhesive resin bonded to the materials. Seventy specimens of hybrid ceramic, leucite-based glass-ceramic, lithium disilicate glass-ceramic, and zirconia-reinforced lithium silicate glass-ceramic were prepared and divided into seven groups according to the surface treatments: Control (C); MEP etching for 60 (MEP60) and 120 (MEP120) s; 5% HF etching for 60 (HF-5%60) and 120 (HF-5%120) s; 9.5% HF etching for 60 (HF-9.5%60) and 120 (HF-9.5%120) s. The Ra was measured using a 3D profilometer. All groups were treated with a universal primer except for the C, MEP60, and MEP120 groups. A self-adhesive resin cement was bonded to all specimens, and the bond strengths were measured using a universal testing machine. All surface treatments increased both Ra and SBS values compared to the control in each material. Neither the duration of surface treatments nor the HF acid concentrations had a statistically significant effect on SBS. Within the limitations of this experimental study, it can be concluded that Monobond Etch & Prime may be a preferable method to achieve high bond strength values.