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Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but severe pediatric condition first described in Europe and the United States in early 2020, shortly after initial reports from the United Kingdom and Italy. Also referred to as Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS), MIS-C was rapidly recognized as a delayed, potentially life-threatening complication of prior SARS-CoV-2 infection. Unlike acute COVID-19, which is often mild or asymptomatic in children, MIS-C is characterized by a profound hyperinflammatory response, with symptoms typically emerging 2 to 5 weeks after the initial infection. The syndrome raised major concerns due to its risk of rapid clinical deterioration and severe organ involvement, particularly affecting the cardiovascular system. Over the past five years, a growing body of research has substantially advanced our understanding of MIS-C, encompassing its pathophysiological mechanisms, clinical presentation, diagnostic criteria, treatment strategies, and long-term outcomes. In view of the persistent epidemiology of COVID-19, this article synthesizes current knowledge within the framework of a personalized medicine approach, highlights recent insights from advanced peer-reviewed studies, and underscores the need for tailored therapeutic strategies to optimize patient care.