Using publicly available single-cell RNA-sequencing datasets, we employed the CITE-seq technique, which combines transcriptomic and epitope profiling, to analyze T cell subpopulations. Our findings revealed a disease-specific expansion of Trm and regulatory T cells (Tregs): PSO lesions showed a higher proportion of Trm cells, while AD was enriched in Tregs. Clustering analysis of CD4+ Trm cells identified disease-specific transcriptional signatures, with cluster 5 predominating in AD and clusters 1 and 4 in PSO. Further analysis of gene expression patterns indicated distinct co-signaling and migratory profiles. Trm cells in AD expressed genes associated with co-stimulatory signaling and tissue egress (e.g., SELL, S1PR1, CCR4), suggesting a migratory phenotype. In contrast, Trm cells in PSO exhibited strong tissue retention, marked by high expression of ITGAE, CD44, and CXCL13. These differences align with clinical observations—diffuse lesions in AD versus well-demarcated, recurrent plaques in PSO. Our study highlights the functional heterogeneity of Trm cells in AD and PSO and underscores their pivotal role in disease progression. These insights may aid in the development of targeted therapies tailored to the unique immunological landscape of each condition. Future studies will validate these transcriptomic findings at the protein level using immunofluorescence-based techniques.