Aim: Document and analyze our experiences from eastern India pertaining to multisystem inflammatory syndrome in children (MISC), which is a novel disease entity with variable presentations and varying treatment guidelines. Materials and methods: Observational cohort study on children diagnosed with MISC by the World Health Organization (WHO) criteria at the Institute of Child Health (ICH) Kolkata from July to December 2020. History, clinical findings, laboratory investigations, including imaging, and response to different therapeutic modalities were noted, and postdischarge follow-up data for 6 months were recorded and subsequently analyzed. Results: A total of 75 children with a median age of 11 years [interquartile range (IQR): 3 years] were included. All presented with fever. 86% had erythematous maculopapular rashes. Gastrointestinal complaints were present in about 30%. Central nervous system (CNS) affection varied from extreme irritability in 63% to drowsiness in 18%. Around 42.67% needed intensive care, and 28% required inotropic support. Cardiac affection was detected in 57.74%, mostly as myocarditis, and 27% had coronary artery dilatations (CAAs). About 20% required respiratory support, and four had to be ventilated. Significant laboratory investigations included neutrophilia, very high C-reactive protein (CRP) (mean 186.8 mg/L), and pro B-type natriuretic peptide (NT-proBNP) (mean 10370 pg/mL). Coronavirus disease 2019 (COVID-19) immunoglobulin (IgG) was positive in 91%. A total of 90.6% received intravenous Ig (IVIg), and 57.3 received methylprednisolone (MP) + IVIg. The dosage of MP varied from 2 to 30 mg/kg; doses were individualized depending on the clinical severity. All of the patients survived and had normalization of cardiac lesions on follow-up. Conclusion: Multisystem inflammatory syndrome in children (MISC) is a hyperinflammatory disease with variable presentations, often requiring intensive care management. Early identification and immediate administration of steroids/IVIg revert the stormy progression, usually without significant residual morbidity.