Various strategies have been explored to stimulate new bone formation. These strategies include using angiogenic stimulants in combination with inorganic biomaterials. Neovascularization during the neo-bone formation provides nutrients along with bone-forming minerals. Therefore, it is crucial to design a bone stimulating microenvironment composed of both pro-angiogenic and osteogenic factors. In this respect, human vascular endothelial growth factor (hVEGF) has been shown to promote blood vessel formation and bone formation. Furthermore, in recent years, whitlockite (WH), a novel phase of magnesium-containing calcium phosphate derivatives that exist in our bone tissue, has been synthesized and applied in bone tissue engineering. In this study, our aim is to explore the potential use of hVEGF and WH for bone tissue engineering. Our study demonstrated that hVEGF and a WH microenvironment synergistically stimulated osteogenic commitment of mesenchymal stem cells both in vitro and in vivo.