Objective To analyze the effect of optimized quality control system and evaluation indicators on the screening efficiency of neonatal genetic metabolic diseases. Methods By utilizing 13 evaluation indices across three dimensions, namely management quality, blood film quality, and diagnosis and treatment quality, the study analyzed the variations in the quality of screening work before the establishment of Zhejiang Quality Control Monitoring and Evaluation Indicators in 2013, after its establishment in 2015, as well as in 2020 and 2023 following subsequent revisions. This analysis aimed to comprehend the actual impact of assessment and management indices on the screening work. Results The screening rate and recall rate of genetic metabolic diseases in newborns in Zhejiang Province between 2013, 2015, 2020 and 2023 were statistically significant by Chi-square test (P<0.05), but there was no statistically significant difference by linear regression test (P>0.05). There were statistically significant differences in the rate of unqualified blood samples, the rate of incomplete collection of unqualified blood samples, the rate of delayed delivery for blood samples and the rate of missing and incorrect blood samples in neonatal genetic metabolic diseases in Zhejiang Province among different years (P<0.05). In 2023, the above indicators all reached the lowest value. After the linear regression test, the rate of unqualified blood samples, the rate of incomplete collection of unqualified blood samples, and the rate of missing and incorrect blood samples showed a downward trend (P<0.05). Chi-square test showed significant differences in diagnosis and treatment rates of congenital hypothyroidism (CH) and phenylketonuria/tetrahydrobiopterin deficiency (PKU/BH4D) at 2, 3 and 4 weeks after birth among different years (P<0.05). After the trend test by linear regression, the 2-week and 4-week diagnostic rates (treatment rates) of CH and the 3-week diagnostic rates (treatment rates) of PKU/BH4D showed an upward trend (P<0.05). Conclusions Establishing and optimizing quantifiable "indicators" can effectively evaluate and improve the efficiency of screening for genetic metabolic diseases in newborns in Zhejiang Province, so as to further strengthen the prevention and control ability of birth defects.