Background: Multisystem inflammatory syndrome in children (MIS-C) is an uncommon illness related with SARS-CoV-2. It generally develops 2-6 weeks after a kid is infected with SARS-CoV-2 and affects many body organs that become inflamed. Objective: This study aimed to investigate the clinical manifestation of multisystem inflammatory syndrome and the effectiveness of different therapeutic modalities. Patients and methods: A prospective cross-sectional observational study was conducted among 75 children with multisystem inflammatory syndrome in Pediatric, Neonatal Intensive Care Unit, Intermediate Care Unit, and Emergency Department at Sohag University Hospital (From June 2022 to February 2024) included 55 confirmed cases and 20 suspected cases. Results: Regarding the reported symptoms, all confirmed cases complained of fever and half of them complained of pulmonary symptoms. 56.4% of cases complained of diarrhea and 1.8% of cases complained of colic. Regarding clinical signs, 45.5% of cases were hypotensive and 52.7% of cases complained of tachypnea. The mean temperature was 38.91 ± 0.49 °C. Regarding heart examination, 50.9% of cases complained of tachycardia. Regarding therapeutic modalities, 36.4% of cases needed combination of antibiotic, solumedrol and IVIG and most of cases (85.5%) received anticoagulants. Conclusion: Early diagnosis and management through routine screening for MIS-C in pediatric patients presenting with prolonged fever, gastrointestinal, respiratory, or cardiovascular symptoms, especially with a history of COVID-19 exposure. Clinical protocols included standardized treatment protocols for MIS-C to ensure timely and effective management.