In this paper, we used first principles to study the 2D honeycomb ZnO monolayer. Though there are a few of researches about the electronic and optical properties of ZnO monolayer, the properties of ZnO monolayer with biaxial strain and vacancy need to clarify. We found oxygen vacancy can be introduced easier than zinc vacancy, which means ZnO monolayer usually shows n-type in practice. The modification by an oxygen vacancy is the most, while a zinc vacancy modifies the properties least. The synergistic effects of oxygen vacancy and strain can tune the optical properties to the visible and solar energy region. On the other hand, zinc vacancy and strain tune the electronic and optical properties less. Our results can be used to explain the related experiments on ZnO monolayer in future. Our paper also provides a theoretical foundation and paves the way for the various applications of 2D ZnO monolayer.