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The diverse clinical manifestations of allergic skin diseases often overlap with other pathologies, posing significant diagnostic challenges. Allergen-specific IgE (sIgE) testing is essential for identifying triggers and personalizing treatments in allergic skin diseases. A retrospective study was conducted on 4,277 medical records of patients with allergic skin diseases who underwent sIgE testing at the HCMC Hospital of Dermato-Venereology, a tertiary referral dermatology center serving Southern Vietnam, from January to December 2024. The results revealed that 64.09% of the patients exhibited sIgE sensitization. House dust mites (D. farinae: 30.91%, D. pteronyssinus: 25.67%) and fire ants (24.06%) were the predominant allergens. Food sensitization was predominantly mild, with almond being the most common (10.26%). Significantly higher sensitization severity was observed in males, young adults (12–35 years), and non-urban residents (p < 0.001). Correlation analysis demonstrated robust co-sensitization and cross-reactivity among aeroallergens, predominantly driven by house dust mites. In conclusion, allergen sensitization profiles are strongly influenced by demographic and geographic factors, with a characteristic pattern observed in Southern Vietnam. Multiplex sIgE testing provides substantial value in disease stratification, prognostic assessment, and the development of personalized treatment strategies in this tropical setting.