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Globally, 150 to 200 million people are exposed to levels of inorganic arsenic (iAs) that are harmful to human health through the ingestion of contaminated drinking water. Exposure to iAs is associated with both cancer and non-cancer endpoints, and a growing body of literature provides evidence for its role as a developmental toxicant. Exposure to iAs during pregnancy has been evaluated in relation to a variety of birth outcomes and is consistently associated with lower birth weight across epidemiological studies. In adults, the risk and severity of iAs-associated health outcomes such as skin lesions is modified by methylation efficiency, which is indicated by the relative proportions of iAs and its metabolites measured in urine. Hence, factors influencing metabolism show promise as identifiers of vulnerable populations and potential therapeutics. Indeed, there is strong evidence for the role of genetic variation and micronutrient status in modifying iAs toxicity in adult populations, but research evaluating factors modulating iAs toxicity during pregnancy—a physiologically dynamic period in which the developing fetus is easily perturbed by exposure to chemicals, malnutrition, and endocrine disruption—is relatively sparse. This dissertation evaluates two factors: genetic variation, namely single nucleotide polymorphisms (SNPs) in genes encoding enzymes related to iAs methylation, and micronutrient status, particularly serum concentrations of protective B vitamins. SNPs in genes encoding enzymes related to iAs methylation and maternal serum concentrations of B vitamins are explored as factors influencing fetal susceptibility to iAs-associated lower birth weight. Data collected from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011-2012) is used to carry out three overarching aims. Findings suggest a protective role for vitamin B12 at the population-level that may be supported by molecular data.