The Antarctic Treaty System (ATS) is now situated in a vastly changed environmental and geopolitical context from the one in which it was conceived and developed. Looking ahead, future trajectories for human activities in the Antarctic and their governance are numerous and uncertain. This necessitates an interdisciplinary examination of the ATS, so that the extent to which it can survive as a successful governance regime in the face of future challenges can be determined, and active changes made accordingly. Here, the foundational values of the ATS – peace, science, cooperation – are shown as a useful basis to evaluate its current challenges. Through detailed case-studies of whaling and IUU fishing, weaknesses that characterise the system at present are exposed. These pertain to exploited ambiguity, avoidance of key issues, misalignment with other international agreements and enforcement. Subsequently, exploitative human activities in the Antarctic by 2050 are considered in terms of the emerging drivers of global change. Given the shortcomings identified, the ATS in its current form is deemed inadequate to deal with such issues. Thus, it cannot survive without amendment beyond 2100. The paper closes with strategic recommendations, directed at addressing each of the current weaknesses, made in the view that a re-focus and reimagination of the ATS’ foundational values could reignite this faultering governance regime.