Methicillin-resistant Staphylococcus aureus (MRSA) is a typical human and animal pathogen, causing various diseases. Importantly, certain MRSA clonal lineages have been found in both food animals and humans that pose great concerns to public health. Nevertheless, we still have limited understanding of how these MRSA clones successfully colonize in different hosts. We aim to understand genetic features that enable MRSA for colonization, such as antibiotic resistant genes, virulence factors, and mobile genetic elements, with an emphasis on the differences between human and animal hosts.