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<i>Background and Objectives</i>: Metagenomic next-generation sequencing (mNGS) is an emerging diagnostic tool used to guide the management of infectious diseases. However, clinical criteria in which there is a clear benefit have not been identified, and more real-world clinical experience is needed to identify patient populations in which mNGS testing may have the most benefit. The aim of this article is to evaluate the utilization of mNGS to determine the impact on clinical practice for pediatric patients. <i>Materials and Methods</i>: This retrospective analysis included pediatric patients that had a mNGS test performed between January 2020 and September 2024. The primary outcome was the clinical impact of the mNGS test on patient management defined as either a positive impact or no impact. Secondary outcomes included test turnaround time, agreement or discordance between conventional testing and mNGS, and hospital length of stay. <i>Results</i>: Forty-six mNGS tests in 42 patients were evaluated. Of 60 organisms identified from the 46 tests, 27 organisms (45%) were considered clinically significant. mNGS had a positive clinical impact in 18 (39.1%) patients, primarily due to antimicrobial modifications (16, 34.8%) and new diagnoses (6, 13.0%). The majority of patients with a positive clinical impact were immunosuppressed (15/18, 83.3%). <i>Conclusions</i>: mNGS demonstrated utility in a subset of pediatric patients, particularly those considered immunosuppressed. Its ability to confirm or exclude infections, particularly fungal infections in this patient population, contributed to its impact. However, its limited benefit in immunocompetent patients underscores the importance of careful patient selection to optimize diagnostic and antimicrobial stewardship.