Background: Apatinib is a small molecule tyrosine kinase inhibitor (TKI) that is taken orally and has high specificity for vascular endothelial growth factor receptor 2 (VEGFR-2). This study explored the efficacy and toxicity of apatinib in patients with metastatic breast cancer (MBC) who failed to respond to multifaceted therapy. Methods: A total of 61 patients with MBC who were unresponsive to previous multifaceted chemotherapy were included in this study. The treatment regimens were either a combination of apatinib and chemotherapy or apatinib administered singly with a dose range of 250 mg every second day to 500 mg per day. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were used as outcome measures. Results: Of the 61 patients, partial response (PR) was observed in 14 patients (23.0%), stable disease (SD) was observed in 30 patients (49.2%), and progressive disease (PD) was observed in 17 patients (27.8%). The DCR was 44/61 (72.1%), and the ORR was 14/61 (23.0%). Of the 44 patients who achieved PR or SD, the median PFS was 4 months and 15 days. Patients with intracranial metastases were found to benefit from apatinib. Furthermore, 11 patients underwent next generation sequencing (NGS) and 5 of these had a P53 mutation. Of those 5 cases, the ORR and DCR were 0% and 20.0%, respectively. Of the 6 cases with wild-type P53, the ORR was 50.0%, and the DCR was 100.0%. Multivariate regression analysis found that hypertension was an independent prognostic factor of better DCR. Conclusions: Apatinib showed good efficacy and manageable toxicity in patients with MBC that had not responded to multifaceted therapy.