This study aimed to comparatively evaluate the effects of various surface treatment protocols on the shear bond strength (SBS) between heat-polymerized polymethyl methacrylate (PMMA) and different CAD/CAM framework materials, including cobalt-chromium (Co-Cr) alloys, ceramic particle-reinforced polyetheretherketone (PEEK), and glass fiber-reinforced composite resin (FRC). A total of 135 disc-shaped specimens were prepared from Co-Cr, PEEK, and FRC materials. Surface treatments specific to each material, including airborne-particle abrasion, sulfuric acid etching, laser irradiation, plasma activation, and primer application, were applied. PMMA cylinders were polymerized onto the treated surfaces, and all specimens were subjected to 30,000 thermal cycles. SBS values were measured using a universal testing machine, and the failure modes were classified. The normality of data distribution was assessed using the Kolmogorov-Smirnov test, and the homogeneity of variances was evaluated using Levene's test. Group comparisons were performed using the Kruskal-Wallis test, and Dunn's post hoc test with Bonferroni correction was applied in cases where significant differences were detected (α = 0.05). The highest SBS values (27-28 MPa) were obtained in the Co-Cr group and in the PEEK groups treated with sulfuric acid and primer. In contrast, the PEEK group with additional laser treatment exhibited a lower SBS value. The untreated PEEK group showed significantly lower SBS (3.9 MPa) compared to all other groups. The Trinia groups demonstrated intermediate SBS values (16.5-17.4 MPa), which exceeded the clinically acceptable threshold of 10 MPa. SEM observations revealed material- and protocol-specific surface responses; plasma-treated specimens maintained topographic integrity, whereas laser-induced surfaces showed localized degradation, particularly following dual-step protocols. Fracture mode analysis indicated that higher SBS values were associated with cohesive or mixed failures. SEM observations suggested that plasma treatment preserved surface morphology more effectively than laser treatment. This study highlights the importance of selecting material-specific surface treatments to optimize bonding between CAD/CAM frameworks and PMMA. Sulfuric acid and primer provided strong adhesion for PEEK, while the addition of laser or plasma offered no further benefit, making such steps potentially unnecessary. Trinia frameworks also showed acceptable performance with conventional treatments. These findings reinforce that simplified conditioning protocols may be clinically sufficient, and indicate that FRC materials like Trinia should be more fully considered for their broader clinical potential in modern CAD/CAM-based prosthetic planning.