Objectives: Acute invasive fungal rhinosinusitis has been associated with high mortality rates. We aimed to explore the contribution of novel detection and treatment methods on the outcome of immunosuppressed children with acute invasive fungal rhinosinusitis. Design: Retrospective observational cohort study. Setting: A tertiary children’s hospital. Participants: The records of all children with a hematologic or oncologic disease who developed AIFR between 2005-2020 were reviewed. Results: Thirty-four patients were included. Aspergillosis and mucormycosis were diagnosed in 20 patients (59%) and 12 patients (35%), respectively. Panfungal polymerase chain reaction (PCR) was associated with a change of treatment in 36% of patients. Aggressive surgical approach was adopted and 71% of the patients underwent multiple surgical procedures. Overall, 26% of patients died of disease, however no disease-specific death occurred since 2012. Diagnosis using panfungal PCR (p=.04) and treatment with novel antifungal medications (p=.017) were significantly associated with disease-specific survival. Conclusions: Enhanced fungal detection using panfungal PCR and treatment with novel antifungal agents, combined with rapid diagnosis and treatment, aggressive surgical approach and better control over the underlying oncological disease, may significantly improve the outcome of immunosuppressed children with acute invasive fungal rhinosinusitis.