The nuclear politics of South Asia – in the context of the protracted India-Pakistan conflict – has become one of the most debated topic of contemporary international systems analysis. During the four decades long US-USSR Cold War rivalry, South Asia was an epicentre of great power politics. The standing of New Delhi and Islamabad and their hostile relationship proved centrally important in the wider context of extra-regional power between the United States and Soviet Union. The importance of both India and Pakistan in the Cold War resulted in the US active involvement in the region and placed eventually both India and Pakistan with the United States. The proliferation of overt nuclear weapons in South Asia further intensified the role of United States in the politics of nuclearized subcontinent. The opening of complex bilateral relations by President Bill Clinton and initiation of a global war on terror by President George W. Bush marked a new chapter in the history of subcontinent for both of the principal contestants of South Asia. Subsequently, the administrations of Obama and Trump continued the policy of bilateralism and generated a plan of de-hyphenation for New Delhi and Islamabad by establishing separate relations with India and Pakistan. The strategic consequences of the US bilateral policy intensified the American role in South Asia, moving India closer to the US, while critically re-examining and re-evluating the standing of Pakistan in the region simultaneously. Hence, the trilateral strategic relations between the United States, India, and Pakistan structured an American South Asian policy that proved ultimately to be perplexing. Indo-US and Pak-US complex relations have proven to be complex and, in past, reflect a dichotomy in American South Asian relations. Now, it is difficult to separate the American role from strategic competition of India and Pakistan. This dissertation is an effort to provide a scholarly dimension to the American South Asian engagement, which encompasses a complex and an extensive record of cooperative and estranged diplomatic interaction. Moreover, this study is an attempt to comprehend the triangular relationship of power between these. The theoretical conception of neorealism is applied to understand the South Asian nuclear arms race and its persistent growth in the presence of extra-regional powers. The interconnectedness of South Asian regional sub-system to greater international system carried the debate in this research which attempted to emphasize particularly the US engagement with India and Pakistan. In the end, the research endeavoured to craft a proposed the future scenarios of US South Asian engagement.