We describe the case of a 43-year-old woman with allergic bronchopulmonary mycosis (ABPM) and severe asthma who improved clinically on mepolizumab with eosinophil suppression but had recurrent mucus plugs, persistent right-middle-lobe atelectasis, rising fractional exhaled nitric oxide (FeNO), and high total IgE levels. Following a switch to tezepelumab, she attained sustained symptom control, no systemic steroid-requiring exacerbations, substantial FeNO and IgE decline, and radiologic reduction of mucus plugs and atelectasis. This case illustrates that residual upstream type 2 activity can persist despite IL-5 blockade, and thymic stromal lymphopoietin (TSLP) inhibition may address this gap by concurrently attenuating multiple effectors. In mucus-predominant allergic bronchopulmonary aspergillosis/ABPM with high FeNO/IgE levels after anti-IL-5 therapy, phenotype- and biomarker-guided sequencing of anti-TSLP antibodies may be considered.