Regenerative interventions have demonstrated promising outcomes in repairing bone defects so far. Considering the incidence, economic burden, and pertaining health-related conditions, extensive efforts have been devoted to the expansion of bone repair medicine research. Given that inevitable drawbacks limit the application of autologous, allogenic, and xenogenic grafts, tissue engineering approaches have been comprehensively explored. Bone tissue engineering (BTE) strives for optimal stimulation of native bone tissue properties to promote clinical outcomes. New horizons in the field of bone tissue engineering entail smart biomaterials, cell sources, whole organ engineering, bio-fabrication technologies, bioreactors, tissue neovascularization, and nanotechnology in BTE. This chapter focuses mainly on strategies and unresolved challenges regarding the maximum resemblance between native bone and artificially fabricated tissue fragments.