The aim of this in vitro study is to evaluate the effect of different acidic media on volumetric wear and surface roughness of CAD/CAM monolithic materials. Forty-eight rectangular specimens were prepared using different CAD/CAM monolithic materials: nanohybrid composite (Grandio Blocks, Voco), resin-based composite (Cerasmart, GC), lithium disilicate (E-Max, Ivoclar), and high-translucency zirconia (Katana STML, Kuraray Noritake). After storage in distilled water at 37 °C for two days, the specimens were tested using a chewing machine with a stainless-steel ball as an antagonist (49N loads, 250,000 cycles). Testing was performed using distilled water, Coca-Cola, and Red Bull as abrasive media. Wear and surface roughness analyses of the CAD/CAM materials were performed using a 3D profilometer and analyzed with two-way analysis of variance and post hoc pairwise comparison procedures. Worn surfaces were examined using scanning electron microscopy. Resin-based materials suffered higher volumetric wear than ceramics (p = 0.00001). Water induced significantly less volumetric wear than the other tested solutions (p = 0.0014), independent of the material tested. High-translucency zirconia showed less surface roughness than all the other materials tested. The selection of monolithic CAD/CAM materials to restore worn dentition due to erosive processes could impact restorative therapy stability over time. Resin-based materials seem to be more influenced by the acidic environment when subjected to a two-body wear test.