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Introduction: Genetic disorders are a common cause of morbidity and mortality in the Pediatric Intensive Care Unit (PICU). Identifying a genetic etiology of disease can lead to targeted therapies, palliative care or subspecialist referrals, and outpatient disease monitoring. Studies have shown benefit of next generation genetic sequencing, either whole exome (WES) or whole genome (WGS), in the PICU. However, studies are often single site, small cohorts, or mixed with neonatal cohorts, leaving pediatric intensivists faced with the question of when to employ WES/WGS. To address this question, we completed a systematic review and meta-analysis with the aim of identifying diagnostic yield and clinical utility of WES/WGS in the PICU population. Methods: A Cochrane approach with a PICOS framework was used to review the literature. Literature search terms included: exome sequencing, genome sequencing, children, pediatrics, and intensive care. Studies included PICU patients undergoing WGS/WES from 2014-2024. Overall, 26 studies with 1,149 patients were analyzed. Outcomes measured included: diagnostic yield, change in clinical management, and turnaround time. Random effects models were fit to obtain point estimates for each outcome measure. Odds ratios were estimated through meta-regression to assess associations between diagnostic yield and age as well as presenting symptoms. Results: 22 studies were analyzed for diagnostic yield (DY) and showed a DY of 38%, 95% CI [0.36-0.41]. 16 studies were included for turnaround time analysis with a mean turnaround time of 6.35 days, 95% CI [4.04-9.97], which improved between 2018 and 2024. Patient age was not a predictor of diagnostic yield or clinical utility. In the 15 studies included, 26% of patients experienced a change in management because of WES/WGS, 95%CI [0.23-0.3]. Meta-regression analysis by presenting symptom did not reach statistical significance but trended for diagnosis of cardiac (OR 1.8, p=0.06) and neurodevelopmental (OR 2.5, p=0.11) etiologies. Conclusions: WES/WGS demonstrates clinical utility in the PICU population, and diagnosing genetic disorders during a PICU admission impacts care. Turnaround time for WES/WGS has continued to improve making it a valuable tool. Further studies are needed to identify which PICU patients would benefit most from WES/WGS.