The rare hyper-inflammatory condition known as "multisystem inflammatory syndrome in children (MIS-C)" develops after a COVID-19 infection. Providing dental treatment for patients with MIS-C can be very challenging due to the immunocompromised condition found in these patients leading to rapid progression of other infections, including dental caries. Currently, there is a lack of information regarding the dental management of patients with MIS-C. This case report presents the multiple dental caries management in a 5-year-old Cambodian boy with MIS-C in a dental chair unit, without general anesthesia. Despite the challenges this case presented, i.e. , the patient's age, hyper-inflammatory condition due to MIS-C, taking several medications, multiple caries lesions, and the language barrier for behavior management, we were able to meet this patient's needs. The patient's dental and physical health were found to be satisfactorily stable with no complications. At the 6-month recall, his overall oral health had dramatically improved. Careful treatment planning along with a multidisciplinary approach is highly recommended in such cases. The important roles of dentists are not only to treat oral infection, but also to approach patients holistically because the body systems are all connected.