Psoriasis and atopic dermatitis (AD) are cutaneous immune-mediated inflammatory diseases (IMIDs) characterized by chronic, progressive conditions influenced by environmental and genetic factors. The exact immune mechanisms driving these diseases are not fully understood, but multi-omics techniques are expected to advance the understanding of skin biology and potentially develop more precise and personalized diagnostic and treatment approaches. This review provides an overview of the current knowledge in genomics, epigenomics, and proteomics of AD and psoriasis. **Genomics:** - **AD:** Genomic studies have identified over 70 genes associated with AD, including *FLG*, *OLOV1*, and *IL-13*. These genes play roles in cutaneous barrier function, innate and adaptive immune responses, and stress responses of keratinocytes. - **Psoriasis:** Over 60% of the disease is heritable, with genetic linkage studies identifying multiple loci. Key loci include *PSORS1*, *PSORS2*, and *PSORS4*, which affect the epidermal barrier, innate and adaptive immune systems, and Th1/Th17 signaling pathways. **Epigenomics:** - **DNA Methylation:** Altered DNA methylation patterns have been observed in AD and psoriasis, affecting genes involved in immune response, inflammatory processes, and epidermal structure. For example, demethylation of *TSLP* and *FCERIG* promoters in AD, and differential methylation of genes like *S100A9* and *PTPN22* in psoriasis. - **Histone Modification:** Histone modifications such as acetylation, phosphorylation, methylation, ubiquitination, and SUMOylation influence gene expression and chromatin structure. Altered histone modifications in AD and psoriasis can affect epidermal differentiation and immune function. **Proteomics:** - Recent studies have identified proteomic profiles that can differentiate psoriasis from other conditions, such as mycosis fungoides, and the correlation between β-defensin 2 and PASI scores in psoriasis. **Mendelian Randomization and Cell Death Pathways:** - Mendelian randomization studies have explored the causal relationships between genetic variants and diseases like AD and psoriasis, identifying risk factors and comorbidities. - Cell death pathways such as ferroptosis, pyroptosis, and cuproptosis have been linked to the pathogenesis of AD and psoriasis, with potential implications for diagnosis and treatment. This review highlights the progress in understanding the genetic and epigenetic mechanisms underlying AD and psoriasis, emphasizing the potential of multi-omics approaches to advance personalized medicine in these complex diseases.Psoriasis and atopic dermatitis (AD) are cutaneous immune-mediated inflammatory diseases (IMIDs) characterized by chronic, progressive conditions influenced by environmental and genetic factors. The exact immune mechanisms driving these diseases are not fully understood, but multi-omics techniques are expected to advance the understanding of skin biology and potentially develop more precise and personalized diagnostic and treatment approaches. This review provides an overview of the current knowledge in genomics, epigenomics, and proteomics of AD and psoriasis. **Genomics:** - **AD:** Genomic studies have identified over 70 genes associated with AD, including *FLG*, *OLOV1*, and *IL-13*. These genes play roles in cutaneous barrier function, innate and adaptive immune responses, and stress responses of keratinocytes. - **Psoriasis:** Over 60% of the disease is heritable, with genetic linkage studies identifying multiple loci. Key loci include *PSORS1*, *PSORS2*, and *PSORS4*, which affect the epidermal barrier, innate and adaptive immune systems, and Th1/Th17 signaling pathways. **Epigenomics:** - **DNA Methylation:** Altered DNA methylation patterns have been observed in AD and psoriasis, affecting genes involved in immune response, inflammatory processes, and epidermal structure. For example, demethylation of *TSLP* and *FCERIG* promoters in AD, and differential methylation of genes like *S100A9* and *PTPN22* in psoriasis. - **Histone Modification:** Histone modifications such as acetylation, phosphorylation, methylation, ubiquitination, and SUMOylation influence gene expression and chromatin structure. Altered histone modifications in AD and psoriasis can affect epidermal differentiation and immune function. **Proteomics:** - Recent studies have identified proteomic profiles that can differentiate psoriasis from other conditions, such as mycosis fungoides, and the correlation between β-defensin 2 and PASI scores in psoriasis. **Mendelian Randomization and Cell Death Pathways:** - Mendelian randomization studies have explored the causal relationships between genetic variants and diseases like AD and psoriasis, identifying risk factors and comorbidities. - Cell death pathways such as ferroptosis, pyroptosis, and cuproptosis have been linked to the pathogenesis of AD and psoriasis, with potential implications for diagnosis and treatment. This review highlights the progress in understanding the genetic and epigenetic mechanisms underlying AD and psoriasis, emphasizing the potential of multi-omics approaches to advance personalized medicine in these complex diseases.