This study aimed to evaluate the association between substance use during pregnancy (SUDP) and dental caries considering the Tooth Development Hypothesis and the Behavioral Hypothesis. This is a Brazilian cohort study conducted on 865 children (12-36 months). Exposure to SUDP was the latent variable and consisted of the use of alcohol, tobacco, and illicit drugs. The dependent variable was the number of dental caries lesions according to the Nyvad criteria. Structural equation modeling was used for analysis, estimating the standardized coefficient (SC) in two models: traditional (1) and with bias-corrected bootstrap estimates (2). The models were adjusted for socioeconomic status (SES), child's age, maternal age, symptoms of minor psychiatric disorders, sugar consumption, feeding, developmental defects of enamel, and gingival bleeding on brushing (GBoB) (α = 5%). SUDP did not affect dental caries. SES (SC