Background <p>Traumatic brain injury (TBI) is the most common type of brain injury and significantly contributes to morbidity and mortality in both adults and children. Diagnosing pediatric head trauma with precision is difficult, particularly for youngsters displaying mild symptoms. Contemporary research has investigated the capacity of biomarkers, including neuron-specific enolase (NSE), to enhance the precision of diagnosis.</p> Objective <p>The objective of this systematic review and meta-analysis was to assess the levels of NSE in pediatrics with head trauma.</p> Methods <p>A comprehensive literature search was performed among PubMed, Scopus, and Embase databases, from the inception to August 17^th, 2024, identifying 963 articles. Any article that evaluated the levels of NSE with any source of sampling in the pediatric population was considered as a possible inclusion. The Standard Mean Difference and confidence intervals of the pooled data were calculated. Also, the robustness of the data was confirmed using sensitivity analysis, and the presence of publication bias was evaluated using funnel plots.</p> Results <p>Following the screening and eligibility validation process, 12 studies were selected, which evaluated 806 participants. Meta-analyses revealed markedly elevated NSE levels in patients as compared to controls (<i>p</i>-value &lt; 0.001), indicating its potential as a biomarker for head injury. Further subgroup analyses demonstrated more pronounced correlations between increased NSE levels and severe trauma (<i>p</i>-value &lt; 0.001). In addition, cerebrospinal fluid samples had significantly higher NSE levels than other sample origins (<i>p</i>-value &lt; 0.001). Elevated levels of NSE were also associated with unfavorable results, as assessed by the Glasgow Outcome Scale (<i>p</i>-value &lt; 0.001).</p> Conclusion <p>The findings emphasize the capacity of NSE as a diagnostic and predictive instrument for pediatric head injury, justifying additional research into its clinical uses.</p>