The emergence and subsequent spread of the novel coronavirus SARS-CoV-2 in 2019 underscore the global impact of viral pandemics. To anticipate and mitigate future pandemics, identifying the key determinants of pandemic potential is essential. In this context, investigating closely related viruses provides valuable insights. Here, we compare four coronaviruses: SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-NL63. We analyze their evolutionary histories, genomic features, animal reservoirs, and interactions with the human immune system. Our comparative analysis indicates that genetic flexibility, efficient adaptation to various hosts, broad potential for interspecies transmission, and the ability to bypass existing immunity collectively shape a virus's pandemic potential. Understanding these determinants will enhance our preparedness for future pandemic threats.