Background Multisystem inflammatory syndrome in children (MIS-C) is a serious health condition that develops from and is linked to coronavirus disease 2019. MIS-C is considered a multi-organ dysfunction involving cardiac, renal, respiratory, hematologic, gastrointestinal and neurological symptoms and groups of signs and symptoms such as rash or bilateral non-purulent conjunctivitis, hypotension or shock and acute gastrointestinal problems, which require immediate therapeutic intervention to prevent the aggravation of the patient’s health condition. MIS-C is relatively new in the field of evidence-based medicine; however, there are several clinical guidelines for good clinical practice. For every disorder, the guidelines have different suggestions. Hence, based on the current status of the evidence, recommendations have been combined to form a unified guideline for therapeutic management. Methods This paper compares and evaluates the current MIS-C-specific clinical practice guidelines (namely, American Academy of Pediatrics, American College of Rheumatology, Helen DeVos Children’s Hospital Foundation, Children’s Hospital of The King’s Daughters, and the Infectious Diseases Society of America). The compiled literature was then assessed by the authors separately, and an algorithm was proposed for each disorder, taking into consideration the various guidelines proposed for the management of the disorder. Results The features of MIS-C patients are unified; this is very helpful in managing its symptoms and decreasing mortality rates. In addition, recommendations for pharmacological treatment for MIS-C symptoms are formulated after cross-comparison across five different guidelines. Conclusions This study provides a general interpretation of the results in the context of other evidence and implications for future research. It proposes a unified guideline based on the current evidence, with the best potential to maintain suitable clinical standards in the Saudi Arabian Ministry of Health.