Multisystem Inflammatory Syndrome in Children (MIS-C), a rare condition, has been reported approximately 2-4 weeks after the onset of COVID-19 in children and adolescents, causing inflammation in multiple systems, including cardiovascular and respiratory, digestive, and central nervous systems. This condition is also known as hyperinflammatory shock, Kawasaki-like disease, and Pediatric Inflammatory Multisystem Syndrome (PIMS). The signs and symptoms include but are not limited to fever, rash, peripheral edema, gastrointestinal symptoms, conjunctivitis, and shock. Thirty-eight studies met our criteria, with a total of 5822 patients. The most affected population was between 5-18 years of age. We noted that MIS-C presented with a wide range of signs and symptoms that overlap with Kawasaki Disease, including high fever, sore throat, malaise, tachypnea, tachycardia, conjunctival injection, mucosal edema, cardiac involvement, and gastrointestinal symptoms. It causes an increase SUMMARY in IL-17A, IL-6, and arterial damage, a distinct difference from Kawasaki disease. The laboratory findings in MIS-C showed an increase in inflammatory markers like CRP, ESR, ferritin, leukocytes, and TNF-α. WHO stated that 23% of affected children with MIS-C had underlying conditions like chronic lung diseases, cardiovascular disease, and immunosuppression. In most affected children, aspirin and IVIG were successful, which resulted in a decrease in the inflammatory markers. We find that MIS-C is a rare, but potentially fatal pediatric complication, after COVID-19 infection. The aim of this article is to study the emerging relationship between COVID-19 and MIS-C in children and adolescents affected by this condition, to discuss the immunological mechanisms, and explore potential therapies.