Abstract: An emerging flavivirus of avian origin, Tembusu virus (TMUV) caused substantial economic losses to the poultry industry since its outbreak in southeastern China in 2010. It continues to pose potential zoonotic risks in the nation. The encoded structural capsid, precursor membrane, and envelope proteins as well as 7 non-structural proteins including NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 were found in the TMUV genome. Although it is known that these encoded proteins mediate viral invasion, replication, and immune evasion, several key issues relating to the lack of high-resolution structure, sufficiently verified protein functions, and clarified mechanisms of cross-host transmission remain to be addressed. Based on recent reports on the structural biology of TMUV, this article reviews the genomic structure and core functions of the encoded proteins associated with virus-host interactions and the existing limitations of research to suggest directions for further studies on high-resolution structure, host interacatomes, and targeted drugs and broad-spectrum vaccines for effective prevention and control of the viral diseases.