Background <p>Prenatal metal exposure and genetics may affect birth size, and genetic factors could modify metal toxicity. However, few studies examined gene–metal interactions on birth size.</p> Methods <p>We used data from 324 mother-infant pairs in the Taiwan Birth Panel Study. Cord blood levels of 16 metals were measured with inductively coupled plasma mass spectrometry, and we selected 13 SNPs related to birth size, folate and metal metabolism. Birth weight, birth length and head circumference were abstracted from medical records. Multivariable generalized linear regression was applied to assess single metal–birth size associations and interactions, and quantile g-computation and Bayesian kernel machine regression were applied for metal mixture analyses.</p> Results <p>Prenatal barium exposure was negatively associated with birth size, whereas prenatal zinc exposure was positively associated with birth size. We observed several metal–SNP interactions on birth size, particularly between cobalt and multiple genetic variants. Genetic variants also modified the effects of metal mixtures on birth size.</p> Conclusions <p>Genetic factors may influence the impact of prenatal metal exposure on birth size. Identifying these gene–environment interactions may help guide precision strategies to reduce metal-related risks in early life.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Elevated prenatal Ba and Zn levels were associated with birth size in opposite directions.</p> </ItemContent> <ItemContent> <p>Genetic variants in folate and metal metabolism modified prenatal metal effects, with the strongest interactions seen for cobalt and folate-pathway variants.</p> </ItemContent> <ItemContent> <p>Metal mixture–birth size associations were most pronounced for the rs10830963 genotype and several other variants.</p> </ItemContent> <ItemContent> <p>Gene–metal interactions can inform precision prenatal risk reduction strategies for metal exposure.</p> </ItemContent> </UnorderedList></p>