Atopic dermatitis (AD), or eczema, is an inflammatory skin disease related to environmental factors. As a heterogeneous disease, it presents with complex phenotypes and endotypes. A variety of intrinsic and extrinsic factors can promote the development of AD. While there has been extensive discussion on environmental exposure at the population and community levels, discourse on exposome at individual levels in AD remains insufficient. For example, allergens, microorganisms, parasites, dietary factors, and psychological factors such as stress and anxiety play important roles in AD development. Microorganisms, in particular, exhibit altered composition and diversity on the skin of AD patients, influencing skin barrier integrity and immune responses. The impact of certain microorganisms, such as fungi and viruses, on AD has garnered increasing attention because of their important role in maintaining skin homeostasis. Dietary factors, including sugar intake and histamine‐rich foods, may modulate AD risk and severity, although findings are controversial. Allergens, particularly house dust mite allergens, and aeroallergens, exacerbate AD symptoms by promoting inflammation and barrier dysfunction. Since AD is often the first step in the atopic march, its primary prevention measures are crucial. Some preventive measures involving microorganisms, diet, and moisturizers remain controversial. Effective preventive strategies necessitate a clear understanding of the complex mechanisms of AD, especially host–microbe–environment interactions. This review summarizes recent advances in understanding various risk and protective factors, as well as primary prevention measures for AD.