Atopic dermatitis (AD) and psoriasis exhibit opposing T-cell polarization patterns and cytokine axes. Dupilumab, a monoclonal antibody targeting the interleukin-4/interleukin-13 (IL-4/IL-13) signaling pathway, has become a first-line biologic for moderate-to-severe AD. However, emerging clinical observations reveal that some patients with AD develop psoriasiform eruptions following biologic therapy, while certain patients with psoriasis may conversely develop eczematous lesions after corresponding biologic treatments. This paradoxical immune response has been termed the "immune drift phenomenon." This review synthesizes current evidence regarding the immunological mechanisms, clinical manifestations, histopathological characteristics, temporal patterns, and therapeutic strategies associated with this phenomenon, with particular emphasis on comprehensive management approaches, including topical therapies, systemic medication adjustments, biologic switching, and targeted small-molecule agents. In particular, it is important to acknowledge the potential limitations of small-molecule inhibitors, such as Janus kinase (JAK) inhibitors, or combination biologic therapies for managing immune drift, including the current lack of robust long-term safety and efficacy data in this specific context. We aim to provide clinicians with evidence-based management recommendations while outlining future research directions.