The physiological and pathological changes in the human body caused by environmental pressures are collectively referred to as the Exposome. Human society is facing escalating environmental pollution, leading to a rising prevalence of associated diseases, including respiratory diseases, cardiovascular diseases, neurological disorders, reproductive development disorders, among others. Vulnerable populations to the pathogenic effects of environmental pollution include those in the prenatal, infancy, and elderly stages of life. Conducting Exposome mechanistic research and proposing effective health interventions are urgent in addressing the current severe environmental pollution. In this review, we address the core issues and bottlenecks faced by current Exposome research, specifically focusing on the most toxic ultrafine nanoparticles. We summarize multiple research models being used in Exposome research. Especially, we discuss the limitations of rodent animal models in mimicking human physiopathological phenotypes, and prospect advantages and necessity of non-human primates in Exposome research based on their evolutionary relatedness, anatomical and physiological similarities to human. Finally, we declare the initiation of NHPE (Non-Human Primate Exposome) project for conducting Exposome research using non-human primates and provide insights into its feasibility and key areas of focus. SYNOPSIS: Non-human primate models hold unique advantages in human Exposome research.