STATEMENT OF PROBLEM: Surface treatments (STs) required for micromechanical interlocking can lead to alterations in the surface characterization and mechanical features of the resin-matrix ceramics (RMCs), which may jeopardize the long-term outcome of an indirect restoration. However, evidence on this issue is lacking. PURPOSE: The purpose of this in vitro study was to assess the influence of different STs on the surface roughness (SR), water contact angle (WCA), and flexural strength (FS) of RMCs. MATERIAL AND METHODS: Two hundred rectangular plates (12×14×1 mm) were prepared from 5 different RMC ingots, including a polymer-infiltrated ceramic network (Vita Enamic [VE]), 2 resin nanoceramics (Lava Ultimate [LU], Grandio Blocks [GB]), a flexible nanoparticle-filled resin (GC Cerasmart [GC]), and a reinforced composite resin (Brilliant Crios [BC]). Plates of each RMC group were further divided into 4 subgroups according to the ST applied: Control, no treatment (C); airborne-particle abrasion with aluminum oxide particles (APA); 2W- and 3W-Er,Cr:YSGG laser irradiations (LI2W, LI3W) (n=10 per ST). The SR (Ra) of each plate was recorded with a contact profilometer. WCAs (θ) of distilled water on the plates were determined by using the sessile-drop method. The FS (MPa) of each plate was measured with a universal testing machine. Data acquired for SR, WCA, and FS were statistically analyzed (α=.05). Weibull statistics were also conducted to determine the reliability of each material. RESULTS: The 2-way ANOVA showed that SR, WCA, and FS values were significantly influenced not only by all tested variables but also by their interaction terms (P<.001). All STs significantly increased the SR values (P<.05). Maximum and minimum SR values were recorded in GC-LI3W (7.06 ±0.16) and GC-C (0.07 ±0.02) groups. After STs, WCA values significantly diminished (P<.05). Maximum and minimum WCA values were recorded in LU-C (61.74 ±2.45) and VE-APA (40.38 ±1.56) groups. All STs significantly reduced the FS values (P<.05). The upper and lower FS bounds were 140.7 ±17.07 and 60.66 ±6.31, respectively, set by VG-C and GC-APA. Weibull distribution indicated that the untreated groups presented the highest m values. Among the treated groups, BC-LI3W demonstrated superior reliability (m=14.04). CONCLUSIONS: APA for LU, LI2W for VG and BC, and LI3W for GC and VE can be preferred. Although APA increased the SR and provided more wettable surfaces, it caused considerable loss of FS. Therefore, LI can be recommended as a safer ST for RMCs.