Tuli Karoo transboundary aquifer (TBA) is shared between Botswana, South Africa and Zimbabwe in the Southern African Development Community (SADC) region. The TBA provides groundwater resources for various economic activities. Irrespective of the value offered by this TBA, there is very little research that has been conducted to improve understanding of the physical system and potential cross-border impacts that can result from exploitation of the aquifer. In the wake of this limited research, this paper uses theoretical background and conceptual understanding to highlight some of the activities that have the potential to cause conflicts within the TBA. This article presents and discusses the current hydrogeological conceptual understanding of the Tuli Karoo TBA system, social and economic activities and their potential impacts on the TBA. Based on the discussions of various scenarios, it can be argued that the potential for groundwater cross-border flow and impacts exist within the TBA. With the ever-increasing and competing demands for fresh water and unpredictable rainfall patterns in the region, the possibility of future conflicts cannot be ruled out. It is hoped that this study can assist in raising awareness about the need to address aspects of sustainable exploitation and management of the TBA.