Allergen-specific memory CD4 T cells are crucial to recrudesce and aggravate allergic asthma. In addition, it was reported that ST2^hiCD44^hi Th2 cells substantially contributed to develop steroid-resistant lung inflammation upon exposure to IL-33. Thus, we hypothesized that steroid resistant-inducing pathogenic Th2 cells develop from allergen-specific memory T cells in IL-33-rich allergic lung microenvironments. To test this hypothesis, we generated allergen-specific memory CD4 T cells, and then treated these mice with IL-33, allergen, or both in each group. We found that airway eosinophilia was declined by steroid when challenged with either IL-33 or allergen alone, while the inflammation became steroid-resistant by the challenge with a mixture of allergen and IL-33. To define underlying mechanisms, we performed single cell transcriptome analysis of allergen-specific CD4 T cells. Unexpectedly, mRNA levels of transcription factors, which are unidentified as Th2-related, such as Epas1 encoding HIF2a, were upregulated in Th2 cluster in allergen rechallenged mice with IL-33 compared to allergen-alone treated. We further tested whether HIF2a is a crucial factor for the differentiation of pathogenic Th2 cells by using retroviral vectors to overexpress this gene. When Epas1-overexpressing Th2 cells were transferred into naïve mice which then were challenged with a mixture of allergen and HDM, it was observed that airway eosinophilia and the numbers of IL-5+ allergen-specific CD4 T cells were unaltered by steroid. Altogether, we propose that Epas1 plays a decisive role in developing steroid resistant-allergic asthma by enhancing the function of secondary effector Th2 cells.