In the wake of the end of the Cold War and disintegration of its bipolar structure, a protracted debate has been seriously intensified about the emergent international systemic transition. Students and practitioners of international relations thought and acted in terms of a highly simplified but very useful picture of world affairs, the Cold War paradigm. This chapter looks at a systematized inquiry with the help of a conceptual framework into the emergent prospects of Indo-US relations in the context of the present systemic transition. It argues that a theoretical framework is the most essential tool, not only for understanding the causal dynamics of contemporary events but also for predicting and pre-empting the future course of events to a certain degree. The probable consequences of the systemic transition are not merely abstract academic puzzles, of interest only to theoreticians.