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Ensuring optimum bond strength during cementation is vital for restoration success, with the practicality of the process being crucial in clinical practice. This study analyzed the effect of a single-step self-etching ceramic primer (MEP) and various surface treatments on the microshear bond strength (µSBS) between resin cement and glass-ceramic or polymer-based ceramic CAD/CAM materials. Specimens were fabricated from leucite-based glass-ceramic (LEU), lithium disilicate glass-ceramic (LDC), resin nanoceramic (RNC), and polymer infiltrated ceramic network (PICN) (<i>n</i> = 160). They were then classified based on the surface treatments (<i>n</i> = 10): control (no treatment); sandblasting with Al₂O₃ (AL); etching with hydrofluoric acid (HF); and MEP application. Scanning electron microscopy was used to evaluate the surface topography. µSBS was measured after cementation and thermocycling procedures. Failure modes were examined with a stereomicroscope. Statistical analysis involved two-way analysis of variance and Tukey HSD tests with a significance level of 0.05. µSBS was significantly influenced by both surface treatment and CAD/CAM material type. The most enhanced µSBS values for each material, regarding the surface treatment, were: LEU and LDC, HF; RNC, AL; PICN, AL or HF. MEP significantly increased the µSBS values of CAD/CAM materials except RNC, yet it did not yield the highest µSBS values for any of them.