The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, has led to over six million deaths worldwide. Understanding what makes a virus capable of causing a pandemic is critical for predicting, preparing, and responding to future pandemics. Here, we analyze the pandemic potential of SARS-CoV-2 and related coronaviruses by systematically comparing viral features and host responses across multiple species. We identify key factors associated with pandemic potential, including viral characteristics such as increased infectivity, immune evasion, or virulence; host factors such as species tropism and abundance; and environmental factors such as temperature and humidity. Our comprehensive comparative analysis provides insights into the determinants of viral pandemic potential and sheds light on the evolutionary forces that contribute to the emergence of highly transmissible and pathogenic viruses.