Atopic dermatitis (AD) or atopic eczema is an increasingly manifested inflammatory skin disorder of complex etiology which is modulated by both extrinsic and intrinsic factors. The exposome includes a person’s lifetime exposures and their effects. We recently reviewed the extrinsic exposome’s environmental risk factors that contribute to AD. The periods of pregnancy, infancy, and teenage years are recognized as crucial stages in the formation of AD, where the exposome leads to enduring impacts on the immune system. However, research is now focusing on the interactions between intrinsic pathways that are modulated by the extrinsic exposome, including genetic variation, epigenetic modifications, and signals, such as diet, stress, and microbiome interactions. As a result, immune dysregulation, barrier dysfunction, hormonal fluctuations, and skin microbiome dysbiosis are important factors contributing to AD development, and their in-depth understanding is crucial not only for AD treatment but also for similar inflammatory disorders.