Objective: To analyze the application value of tandem mass spectrometry (MS/MS) in screening inherited metabolic diseases (IMDs) in newborns in Shangrao. Methods: A total of 82,158 newborns who received IMDs screening using tandem mass spectrometry in Shangrao from December 2022 to December 2024 were selected. Their positive results in initial screening, blood amino acid and acylcarnitine concentrations were statistically analyzed. Secondary testing and other testing methods were used to confirm the diagnosis of positive cases in initial screening. Results: Among the 82,158 newborns, 1,306 were positive in initial screening, with a positive rate of 1.59%. Among the positive cases, 42 were confirmed by secondary examination with imaging and laboratory tests, approximately 1/1,956, with a rate of 0.05% and a false positive rate of 1.54%. There were 7 cases of abnormal organic acid metabolism, 9 cases of abnormal fat metabolism, and 26 cases of abnormal amino acid metabolism. Among the 1,306 newborns positive in initial screening, 48 were confirmed positive by MS/MS, and 43 were comprehensively diagnosed as IMDs. The diagnostic accuracy, specificity and sensitivity of MS/MS were 99.62% (1,301/1,306), 99.60% (1,258/1,263), and 100% (43/43), respectively. 43 newborns diagnosed with IMDs were followed up for 6-24 months. Among them, 39 newborns had no obvious clinical symptoms, and the other 4 newborns received standardized treatment, follow-up, and regular examinations, with a visit rate of 100%. Conclusion: MS/MS demonstrates high value in screening IMDs in newborns in Shangrao, with high diagnostic sensitivity and specificity. It is recommended to promote the use of MS/MS as a routine screening method for newborns to enhance the prevention and control of IMDs.