With over 500 million confirmed cases and 6.2 million deaths worldwide, the novel coronavirus has highlighted the underlying disparities in healthcare, unpreparedness to deal with a new disease and the need for monitoring and surveillance for a post-infectious syndrome as well as complicated diseases. Initially, children were thought to be spared but reports of a new phenomenon manifesting as Kawasaki-like disease, toxic shock syndrome, and multi-system inflammatory syndrome, which developed after a few weeks of severe COVID-19 infection, emerged in the pediatric population. As the pandemic progressed, increased prevalence of multi-system inflammatory syndrome in children (MIS-C) related to COVID-19 was seen in non-Hispanic blacks, Asians, and Latinos as compared to the white population drawing attention to a possible role of ethnicity and socio-economic disparities. The CDC currently reports that 31% of MIS-C cases were seen in Black Non-Hispanics and 26% in Latinos, who were historically more affected in previous pandemics. Furthermore, MIS-C cases in developing countries showed higher mortality as compared to high-income countries, which points toward the role of social determinants of health and limitations in a low-resource set up in increasing the disease burden of MIS-C, which should be treated as a public health emergency. Our review highlights the role of ethnicity, socio-economic factors, comorbidities, and differences in populations affected by MIS-C in high-income vs. low- and middle-income countries.