Atopic dermatitis is a chronic, heterogeneous inflammatory skin disorder affecting up to 20% of children and 2–10% of adults worldwide. In most patients, disease pathogenesis is driven by a type 2 immune response mediated by interleukin-4 and interleukin-13. Elevated type 2 biomarkers, including eosinophils, CCL17, and fractional exhaled nitric oxide, identify atopic dermatitis phenotypes that are highly dependent on these cytokines and responsive to their inhibition. Severe atopic dermatitis substantially impairs quality of life and, in a subset of patients, follows a treatment-refractory course associated with significant psychosocial burden. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha, inhibits IL-4 and IL-13 signalling and represents a major therapeutic advance. Despite its proven efficacy and favourable safety profile, responses remain heterogeneous and difficult to predict. Consequently, the identification of reliable prognostic and predictive biomarkers has emerged as a key research priority. Advances in transcriptomics, proteomics, and metagenomics, combined with growing clinical evidence, support the development of integrated biomarker panels to guide personalised therapy. Clinical studies consistently demonstrate that dupilumab significantly reduces disease severity in many patients, underscoring the need for validated predictive markers. This review critically examines current evidence on biomarkers associated with atopic dermatitis pathophysiology and response to dupilumab, highlighting their predictive potential and relevance for routine clinical practice, and implications for precision medicine in the management of severe atopic dermatitis.