Recently, and after its emergence in Wuhan, China, the COVID-19 infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread in almost every country in the world. This infection has appeared as a subject of intensive debate and concern among most of the government’s public health systems, researchers, and policymakers. The severity of this zoonotic disease upshot a pandemic situation, which has a long-term impact on the personal, behavioral, social, and economic, as well as on the political and state affairs. Variations in COVID-19 severity made the situation more critical to elucidate the genomics, and genetic pathways linked to susceptibility and transmission of SARS-Cov-2 infection. The current study aimed to shed some light on SARS-Cov-2 infection and COVID- 19 introduction, as well as the evolutionary history, structure, pathophysiology, genetic modulation, diagnosis, and treatment, in order to provide insight into pandemic flinch, its emergence, and progression around the world. The current study also provides a summary of the near future possibility of developing the appropriate medication for COVID-19 treatment and management through the identification of new therapeutic target molecules, including vaccine development and appropriate preventive and control measures.