Aside from the need to confirm our in-vitro results in corresponding in vivo models, collectively, our findings show that tomatine inhibits cell viability as well as the invasive behavior of MM cell lines, and, more importantly, displays valuable antiangiogenic and vascular disrupting effects only in experimental conditions that mimic a proangiogenic tumor microenvironment, perhaps by affecting the ER/p-eIF2α/VEGF axis of tumor angiogenesis. The gene discussed is VEGFA; the disease is neoplasm.