ABSTRACT RNA N1‐methyladenosine (m1A) methylation is dynamically regulated by methyltransferases (TRMT6/61/61B/10C), demethylases (ALKBH1/3), and binding proteins (YTHDF1/2/3), which collectively fine‐tune gene expression through site‐specific modifications. Exogenous environmental factors such as persistent organic pollutants, heavy metals, and radiation can trigger cellular oxidative stress and stimulate the secretion of reactive oxygen species and senescence‐associated secretory phenotypes. The concurrent accumulation of these damaging agents, along with dysregulation of intracellular conditions including temperature, pH, and divalent metal ion concentrations under pathological states, disrupts m1A methylation and alters the expression of associated genes, ultimately leading to adverse cellular outcomes. In addition, we searched a large number of literature and found that m1A methylation exhibits elevated levels in neurodegeneration, ischemia–reperfusion injury, and hepatocellular and bladder cancer, whereas decreased levels are observed in Alzheimer's disease and myocardial infarction. Correspondingly, methyltransferases and binding proteins involved in m1A modification are generally upregulated across multiple disease contexts. We propose that m1A methylation serves as a molecular sensor for environmental–cell interactions, dynamically regulating gene expression through regulators and exerting bidirectional control in disease processes. Given its regulatory versatility, m1A modification holds promise for applications in toxicological risk assessment, precision medicine, and the development of targeted therapies against exogenous factor–induced pathologies.