This study integrates multidimensional computational approaches-network toxicology, machine learning, molecular docking, and molecular dynamics simulation-to systematically elucidate the toxic mechanism by which the environmental pollutant diisononyl cyclohexane-1,2-dicarboxylate (DINCH) contributes to atherosclerosis. By jointly mining multiple databases, we obtained 246 targets common to DINCH and atherosclerosis. LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) then identified 8 significantly upregulated core targets (CSF1R, CD36, CCL3, CCR2, ADAM8, TLR1, CTSS, and MMP1). Functional enrichment analysis showed that these core targets were significantly associated with key signaling pathways, including lipid and atherosclerosis, the PPAR signaling pathway, the PI3K-Akt signaling pathway, and the AGE-RAGE signaling pathway in diabetic complications. Differential gene analysis confirmed that these genes were significantly upregulated in diseased tissues, and receiver operating characteristic (ROC) analysis demonstrated excellent diagnostic performance (AUC = 0.87-0.96). Immune cell infiltration analysis further revealed a strong association between the core targets and immune cell populations, notably macrophages and T cells. Molecular docking and molecular dynamics simulations showed that DINCH had high affinity for the core targets, and its binding to CCR2 was the most stable (binding free energy = -7.6 kcal/mol). The final AOP framework systematically presented the cascade by which DINCH may contribute to atherosclerosis through metabolic disruption and immune activation. This study provides new mechanistic insights into the development of DINCH-induced atherosclerosis and offers a theoretical basis for health risk assessment of environmental pollutants.