Abstract Introduction Central nervous system (CNS) infections pose significant health challenges, particularly in low- and middle-income countries (LMICs), due to high morbidity and mortality rates. Rapid and accurate diagnosis is essential for effective treatment to prevent adverse outcomes. Traditional culture-based diagnostics are often slow and lack specificity. This study evaluates the BioFire® FilmArray® Meningitis/Encephalitis (FAME) Panel against standard diagnostics in Vietnam to assess its clinical impact and suitability for local epidemiology. Methods We conducted a prospective study involving 330 patients with suspected CNS infections at four hospitals in northern Vietnam from July 2022 to April 2023. CSF samples were analysed using routine culture methods and FAME. We compared pathogen detection rates and assessed the potential clinical impact of FAME results on patient management. Results Of the 330 CSF specimens, 64 (19%) were positive by either conventional diagnostics (n=48) and/or FAME (n=33). The agreement between FAME and conventional diagnostics was 87%. Key pathogens Mycobacterium tuberculosis (n=7), Klebsiella pneumoniae (n=5), Streptococcus suis (n=5), Epstein-Barr virus (n=3), Acinetobacter baumannii (n=1), and Trichosporon asahii (n=1) were not detected by FAME. Classical meningitis parameters-clinical symptoms, altered glucose, protein, and pleocytosis- were good predictors of FAME positivity, indicating their utility in optimizing local diagnostic algorithms. Conclusion FAME complements traditional diagnostics by offering rapid and broad pathogen detection, crucial for timely and appropriate therapy. However, its effectiveness varies with local epidemiology, and it should not replace conventional methods entirely. Tailoring diagnostic panels to regional pathogen prevalence is recommended to enhance diagnostic accuracy and clinical outcomes in LMICs.