Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, with poor prognosis due to its resistance to therapy. Small molecule drugs, such as MRTX1133, a KrasG12D inhibitor, has shown promise in targeting key drivers of PDAC, yet their efficacy is often hindered by metabolic rewiring associated with the epithelial-to-mesenchymal transition (EMT). In this study, we report an oxygen microsensor for real-time tracking of metabolic shifts in PDAC cell lines during MRTX1133 treatment. We find that drug-resistant EMT+ cells exhibit higher oxygen consumption rates and thus a delayed increase in extracellular oxygen concentration compared to drug-sensitive cells, indicating distinct metabolic profiles linked to therapeutic resistance. These findings suggest that real-time metabolic monitoring could serve as a predictive tool for identifying resistant subpopulations, offering a potential strategy for optimizing therapeutic interventions in PDAC.