This study aims to compare the shear bond strength (SBS) of a direct resin composite to CAD-CAM resin composite blocks treated with different surface treatments: micromechanical, chemical or a combination of both. Eight CAD-CAM resin composite blocks, namely Brilliant Crios, Cerasmart 270, Vita Enamic, Grandio block, Katana Avencia, Lava Ultimate, Tetric CAD and Shofu Block HC were chosen. The micromechanical surface treatment protocols tested were hydrofluoric acid, polyacrylic acid or sandblasting, and the chemical one was a universal primer. These treated CAD-CAM blocks were tested to determine the SBS of a light-curing composite resin Z100 bonded to their surface. Two-way ANOVA followed by Tukey’s post hoc test was used to investigate the difference in SBS. Failures were analyzed by Fisher’s exact test. Bonding interfaces were examined by scanning electron microscopy. The micromechanical surface treatments give the highest SBS values: sandblasting appears to be the most efficient procedure for dispersed filler composite blocks, while hydrofluoric acid etching is preferable for polymer-infiltrated ceramic network (PICN) blocks. The use of universal primer does not improve SBS values on dispersed filler composite blocks. For PICN blocks, the use of universal primer significantly increases SBS values when combined with hydrofluoric acid etching.