Due to the continually growing complexity demands of integrated circuits (ICs), electronic design automation flows must enable efficient design of ICs through design entry at higher abstraction levels. IC design has gradually transitioned from circuit-level to logic-level, register-transfer level, behavioral-level and now electronic-system-level design abstractions. Higher abstraction levels are required to make large scale design entry feasible, but design and development of tools for such design entry poses significant research challenges. The research community has tackled these problems individually by decomposing the synthesis problem into a series of sequential stages. Although this strategy has proven successful and led to the rise of commercial synthesis tools, necessary major improvements require optimizing the interactions and interdependencies between these stages. In this paper, we discuss challenges and opportunities for optimizing inter-stage interactions, and present results of four example works that target these interactions.