This review discusses the application of multi-omics approaches in improving the diagnosis and treatment of atopic dermatitis (AD) and psoriasis, two chronic immune-mediated inflammatory skin diseases. The study highlights the importance of integrating genomics, epigenomics, and proteomics to better understand the underlying mechanisms of these conditions and develop more precise and personalized therapeutic strategies. The review summarizes current knowledge on the genetic, epigenetic, and proteomic profiles of AD and psoriasis, emphasizing the role of immune pathways, genetic predispositions, and environmental factors in disease development. It also discusses recent findings, such as proteomic profiles that help differentiate psoriasis from mycosis fungoides and the correlation between β-defensin 2 and the Psoriasis Area and Severity Index (PASI) and its response to secukinumab treatment. The review notes that while much remains to be discovered, recent evidence has provided valuable insights into the pathogenesis of these diseases. The study also explores the role of various omics technologies, including proteomics, single-cell transcriptomics, and spatial transcriptomics, in uncovering new biological mechanisms. Additionally, it discusses the genetic and epigenetic factors involved in AD and psoriasis, including the role of genes such as FLG, IL-13, and IL-4, as well as the impact of epigenetic modifications like DNA methylation and histone modifications on disease susceptibility and progression. The review concludes that multi-omics approaches offer a promising avenue for advancing our understanding of these diseases and developing more effective diagnostic and therapeutic strategies.This review discusses the application of multi-omics approaches in improving the diagnosis and treatment of atopic dermatitis (AD) and psoriasis, two chronic immune-mediated inflammatory skin diseases. The study highlights the importance of integrating genomics, epigenomics, and proteomics to better understand the underlying mechanisms of these conditions and develop more precise and personalized therapeutic strategies. The review summarizes current knowledge on the genetic, epigenetic, and proteomic profiles of AD and psoriasis, emphasizing the role of immune pathways, genetic predispositions, and environmental factors in disease development. It also discusses recent findings, such as proteomic profiles that help differentiate psoriasis from mycosis fungoides and the correlation between β-defensin 2 and the Psoriasis Area and Severity Index (PASI) and its response to secukinumab treatment. The review notes that while much remains to be discovered, recent evidence has provided valuable insights into the pathogenesis of these diseases. The study also explores the role of various omics technologies, including proteomics, single-cell transcriptomics, and spatial transcriptomics, in uncovering new biological mechanisms. Additionally, it discusses the genetic and epigenetic factors involved in AD and psoriasis, including the role of genes such as FLG, IL-13, and IL-4, as well as the impact of epigenetic modifications like DNA methylation and histone modifications on disease susceptibility and progression. The review concludes that multi-omics approaches offer a promising avenue for advancing our understanding of these diseases and developing more effective diagnostic and therapeutic strategies.