The latest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron (B.1.1.529) has ushered panic responses around the world due to its contagious and vaccine escape mutations. The essential infectivity and antibody resistance of the SARS-CoV-2 variant are determined by its mutations on the spike (S) protein receptor-binding domain (RBD). However, a complete experimental evaluation of Omicron might take weeks or even months. Here, we present a comprehensive quantitative analysis of Omicron's infectivity, vaccine-breakthrough, and antibody resistance. An artificial intelligence (AI) model, which has been trained with tens of thousands of experimental data points and extensively validated by experimental data on SARS-CoV-2, reveals that Omicron may be over ten times more contagious than the original virus or about twice as infectious as the Delta variant. Based on 132 three-dimensional (3D) structures of antibody-RBD complexes, we unveil that Omicron may be twice more likely to escape current vaccines than the Delta variant. The Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) from Eli Lilly may be seriously compromised. Omicron may also diminish the efficacy of mAbs from Celltrion and Rockefeller University. However, its impact on Regeneron mAb cocktail appears to be mild.