The emergence of SARS-CoV-2 variants has further raised concerns about viral transmission. A fundamental understanding of the intermolecular interactions between the coronavirus and different surfaces is needed to address the transmission of SARS-CoV-2 through respiratory droplet-contaminated surfaces or fomites. The receptor-binding domain (RBD) of the spike protein is a key target for the adhesion of SARS-CoV-2 on the surface. To understand the effect of mutations on adhesion, atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) was used to quantify the interactions between wild-type, Omicron, and XBB with several surfaces. The measurement revealed that RBD exhibits relatively higher forces on paper and gold surfaces, with the average force being 1.5 times greater compared to that on plastic surface. In addition, the force elevation on paper and gold surfaces for the variants can reach ∼28% relative to the wild type. These findings enhance our understanding of the nanomechanical interactions of the virus on common surfaces.