Background: The addition of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) to chemotherapy and/or hormonal therapy for advanced breast cancer management remains controversial. We reviewed data from RCTs and conducted a meta-analysis to systematically evaluate the benefits and risks of adding VEGFR-TKIs therapy to standard treatment for advanced breast cancer. Methods: PubMed, Web of Science and ASCO and ESMO databases were searched. Eligible studies were RCTs that compared treatment outcomes (OS, PFS and/or TTP) of standard therapy with or without addition of VEGFR-TKIs in advanced breast cancer. Study endpoints included OS, PFS, and grade 3 or above adverse events (AEs). Pooled HRs for survival outcomes and RRs for dichotomous data with 95% CI were calculated using comprehensive meta-analysis (v2). Results: Nine eligible trials comprising a total of 2,206 patients were identified. VEGFR-TKIs included sorafenib (3), sunitinib (2), vandetanib (2), axitinib (1), and motesanib (1), and standard therapies included paclitaxel (2), docetaxel (3), gemcitabine (2), capecitabine (2), and fulvestrant (1). The addition of VEGFR-TKIs did not improve OS (HR 1.01; 95% CI 0.88-1.16, P = 0.889) or PFS (HR 0.87; 95% CI 0.72-1.03, P = 0.109). However, adding VEGFR-TKIs increased the risk of hypertension (RR 3.38; 95% CI 1.37-8.30, P = 0.008), rash (RR 2.64; 95% CI 1.14-6.14, P = 0.024), hand-foot syndrome (RR 4.73; 95% CI 1.33-16.81, P = 0.016), and mucosal inflammation (RR 2.41, 95% CI 1.10-5.28, P = 0.028), but not the risk of vomiting, diarrhea or neutropenia. Conclusions: Our meta-analysis demonstrates that adding VEGFR-TKIs to standard treatment in advanced breast cancer did not improve treatment outcomes, and increased the risk of certain severe AEs, such as hypertension, rash, and hand-foot syndrome and mucosal inflammation. Because of patient and treatment heterogeneities among the trials, eg., ER/PR/HER2 status, locally advanced vs. metastatic, first vs. any line of therapy, additional studies are needed to further evaluate the efficacy of VEGFR-TKIs in advanced breast cancer.