Here, we investigated the role of fibroblast growth factor (FGF) signaling in resistance to CDK4/6 inhibitors and endocrine therapy, as well as the effects of tasurgratinib, an FGFR1–3 selective inhibitor, on drug resistance in preclinical ER+/HER2− breast cancer cell lines and patient-derived xenograft models. Here, ESR1 is linked to breast cancer.