Here, our results presented a novel finding that DPP-4i can reprogram tumor microenvironment that facilitates murine breast cancer metastasis by interacting with cancer cells via a ROS–NRF2–HO-1–NF-кB–NLRP3 axis, providing an immune mechanistic insight into the dark side of DPP-4i in BC progression. Here, HMOX1 is linked to breast cancer.