Angiogenesis is a critical process in tumor development, and abnormal vasculature from tumor angiogenesis contributes to drug resistance in breast cancer by increasing tumor hypoxia, reducing drug concentrations, and affecting immune mechanisms. Anti-angiogenic therapy can counteract these resistance factors by promoting vascular normalization. Combining anti-angiogenic therapy with chemotherapy, targeted therapy, or immunotherapy is a promising approach to overcome drug resistance in breast cancer. This review discusses the mechanisms of angiogenesis and drug resistance in breast cancer, the role of the hypoxic tumor microenvironment, drug distribution, and immune mechanisms. It also summarizes specific anti-angiogenic drugs and studies on reversing drug resistance. The potential mechanisms of these interventions are discussed, and the clinical application of anti-angiogenic therapy to overcome breast cancer treatment resistance is highlighted. Tumor angiogenesis involves the activation of transcription factors like HIF-1α in the hypoxic tumor environment, leading to endothelial cell proliferation and migration via growth factors such as VEGF and PDGF, resulting in a disordered tumor vasculature. VEGF and VEGFR are crucial for angiogenesis, with VEGF-A binding to VEGFR2 promoting angiogenesis through pathways like MAPK and PI3K. PDGF and PDGFR also play roles in angiogenesis, with PDGFR-β significantly expressed in breast cancer cells. EGF and EGFR are involved in angiogenesis through pathways like MAPK and PI3K. Other factors like FGF, HGF, IGF, and TGF-β also contribute to angiogenesis. Hypoxia induces HIF-1α, which promotes angiogenesis by activating transcription factors like Twist, Snail, and ZEB2. Hypoxia also promotes EMT, leading to tumor angiogenesis. Tumor angiogenesis affects drug distribution and the immune system, with VEGF inhibiting antigen presentation and T-cell activation. Angiogenesis-related factors promote an immunosuppressive tumor microenvironment. Anti-angiogenic therapy can reverse drug resistance by normalizing blood vessels, reducing hypoxia, and improving drug efficacy. Tumor vascular normalization, a novel concept, can normalize tumor blood vessels, promote drug delivery, and prevent or reverse drug resistance. Anti-angiogenic therapy can enhance the effectiveness of immunotherapy by improving immune cell infiltration and activation. Drug resistance in breast cancer is influenced by factors like apoptosis, ferroptosis, drug efflux systems, and tumor angiogenesis. Hypoxia induces drug resistance by promoting the expression of MDR1, MRP1, and BRCP. Hypoxia also promotes the acidic microenvironment, which affects drug efficacy and promotes breast cancer stem cell phenotypes. Hypoxia-induced resistance is mediated by HIF-1α, which activates ABC transporters and promotes drug efflux. Anti-angiogenic therapy can reverse drug resistance by inhibiting HIF-1α and improving drug delivery.Angiogenesis is a critical process in tumor development, and abnormal vasculature from tumor angiogenesis contributes to drug resistance in breast cancer by increasing tumor hypoxia, reducing drug concentrations, and affecting immune mechanisms. Anti-angiogenic therapy can counteract these resistance factors by promoting vascular normalization. Combining anti-angiogenic therapy with chemotherapy, targeted therapy, or immunotherapy is a promising approach to overcome drug resistance in breast cancer. This review discusses the mechanisms of angiogenesis and drug resistance in breast cancer, the role of the hypoxic tumor microenvironment, drug distribution, and immune mechanisms. It also summarizes specific anti-angiogenic drugs and studies on reversing drug resistance. The potential mechanisms of these interventions are discussed, and the clinical application of anti-angiogenic therapy to overcome breast cancer treatment resistance is highlighted. Tumor angiogenesis involves the activation of transcription factors like HIF-1α in the hypoxic tumor environment, leading to endothelial cell proliferation and migration via growth factors such as VEGF and PDGF, resulting in a disordered tumor vasculature. VEGF and VEGFR are crucial for angiogenesis, with VEGF-A binding to VEGFR2 promoting angiogenesis through pathways like MAPK and PI3K. PDGF and PDGFR also play roles in angiogenesis, with PDGFR-β significantly expressed in breast cancer cells. EGF and EGFR are involved in angiogenesis through pathways like MAPK and PI3K. Other factors like FGF, HGF, IGF, and TGF-β also contribute to angiogenesis. Hypoxia induces HIF-1α, which promotes angiogenesis by activating transcription factors like Twist, Snail, and ZEB2. Hypoxia also promotes EMT, leading to tumor angiogenesis. Tumor angiogenesis affects drug distribution and the immune system, with VEGF inhibiting antigen presentation and T-cell activation. Angiogenesis-related factors promote an immunosuppressive tumor microenvironment. Anti-angiogenic therapy can reverse drug resistance by normalizing blood vessels, reducing hypoxia, and improving drug efficacy. Tumor vascular normalization, a novel concept, can normalize tumor blood vessels, promote drug delivery, and prevent or reverse drug resistance. Anti-angiogenic therapy can enhance the effectiveness of immunotherapy by improving immune cell infiltration and activation. Drug resistance in breast cancer is influenced by factors like apoptosis, ferroptosis, drug efflux systems, and tumor angiogenesis. Hypoxia induces drug resistance by promoting the expression of MDR1, MRP1, and BRCP. Hypoxia also promotes the acidic microenvironment, which affects drug efficacy and promotes breast cancer stem cell phenotypes. Hypoxia-induced resistance is mediated by HIF-1α, which activates ABC transporters and promotes drug efflux. Anti-angiogenic therapy can reverse drug resistance by inhibiting HIF-1α and improving drug delivery.