Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory and immunosuppressed condition affecting children exposed to COVID-19. MIS-C has been associated with an over-exaggerated innate and adaptive immune response characterized by a 'selective' cytokine production and T cell suppression. As COVID-19 information has evolved, the knowledge and field surrounding MIS-C is ever evolving. Thus, a comprehensive clinical review that concisely presents current literature findings regarding common clinical presentations and comparisons with similar conditions, associations with the COVID-19 vaccine effects and relevant epigenetic markers and evaluates treatment and long-term outcomes to help guide future studies is needed and provided.