The aim of this study is to present the characteristics and a comparison of four different commercial materials dedicated to the CAD/CAM technique in dentistry, all of which can be classified as ceramic materials. Its purpose is also to evaluate the impact of surface treatment on the cytotoxicity and microbiological properties of the materials. The CAD/CAM technique has a perpetually growing role in modern reconstructive dentistry. It requires a material’s possession of peculiar characteristics, such as mechanical resistance, durability, functionality (similar to natural tissues), good aesthetics and biocompatibility. To critically evaluate a biomaterial, both manufacturer claims and in vitro tests should be considered. Further steps of evaluation may include animal tests and clinical trials. There are certain attributes of biomaterials that may be modified by surface treatment that can be crucial to the clinical success of the material. The evaluated materials were Vita Suprinity (VITA-Zahnfabrik, Germany), Vita Mark II (VITA-Zahnfabrik, Germany), Celtra Duo (Dentsply Sirona, USA) and Empress Cad (Ivoclar Vivadent, Liechtenstein). They are available in the form of prefabricated blocks of various diameters and are popular among operators performing clinical procedures using CAD/CAM. Standardized blocks of each material were prepared. Half of them had their surface polished. Further, half of all the samples were covered by a nano-copper layer. The samples were evaluated for cytotoxicity, presented on a 0–4 scale, adhesion susceptibility and potential of forming a biofilm on their surface. Physicochemical properties such as the water contact angle (WCA) were evaluated for the tested materials. The influence of copper coating on cytotoxicity cannot be unequivocally stated or denied. Surface polishing did not affect the materials’ cytotoxicity, but it increased the WCA of all materials and, therefore, their hydrophobicity. Different degrees of adhesion ability and biofilm formation were dependent on the species of microorganisms and properties of the dental materials.