Context: COVID-19 and influenza COINFECTION may increase mortality and morbidity during the COVID-19 pandemic. Recognizing the differences and similarities between COVID-19 and influenza helps us diagnose and treat these 2 diseases. Accordingly, we aimed to compare virologic, clinical, paraclinical, and radiological features and prophylactic and therapeutic management of SARS-CoV-2 and influenza infections. We also provided an algorithmic approach to the diagnosis and treatment of SARS-CoV-2 and influenza COINFECTION in children. Evidence Acquisition: Electronic databases, including Cochrane Collaboration, PubMed, Google Scholar, and EMBASE, were searched for the articles published in English language using the following keywords: “ influenza virus, ” “ SARS-CoV-2 virus, ” “ COVID-19, ” “ comparison, ” “ COINFECTION, ” “ management, ” “ treatment, ” “ antiviral therapy, ” “ vaccines, ” “ children, ” and “ adults. ” Boolean operations (AND and OR) were used to refine the search. No date limitation was applied. Results: SARS-CoV-2 and influenza are both RNA viruses with different receptors. The reproductive rate of SARS-CoV-2 is higher than influenza. Patients with SARS-CoV-2 infection, particularly adults, have higher rates of anosmia/ageusia. Organ involvement occurs more frequently in COVID-19 cases, and multisystem inflammatory syndrome in children (MIS-C) occurs especially in children. Disease severity, excessive immune response, and mortality are higher in SARS-CoV-2. Radiological peripheral lesions and ground-glass appearance are characteristic of COVID-19 infection. It is important to rule out influenza and SARS-CoV-2 infection in patients with respiratory problems during the pandemic. Timely prescription of currently available antiviral drugs is essential. Conclusions: Treatment of patients suspected of having a COINFECTION is determined by the patient’ s condition and polymerase chain reaction (PCR) evaluation.