Thyroid homeostasis is essential for human health, and arsenic (As) and mercury (Hg) have drawn considerable attention due to their bioaccumulation and potential health risks. However, evidence on their thyroid-disrupting effects remains inconsistent and largely derived from cross-sectional studies, hindering causal inference and risk integration. Here, a meta-analysis was first conducted, which confirmed that both As (Cohen’s d = 0.45, 95% CI: 0.10, 0.81) and Hg (Cohen’s d = 0.40, 95% CI: 0.16, 0.65) exposure were associated with an increased risk of thyroid dysfunction. To further clarify temporality, we analyzed prospective cohort data from 800 adult women in Jiangsu, China. Results showed that As exposure was linearly and positively associated with free thyroxine (FT4) (β = 0.19, 95% CI: 0.01, 0.37), while Hg showed an inverted U-shaped dose–response relationship with FT4 levels. Based on the above epidemiological evidence, we further integrated in vivo and in vitro evidence from published related literature, applied the Targeted Risk Assessment for Environmental Chemicals (TRAEC, ver.1.1) strategy, and obtained final scores of 7.79 for As and 7.09 for Hg (out of 10), indicating a moderate level of thyroid-related health risk. Collectively, these findings suggest that As and Hg exposure may disturb thyroid function, supporting the need for targeted mitigation and further mechanistic research.