External State Actor (ESA) influence will fuel a variety of Hemispheric challenges in the 21st century. These non-Hemispheric nations vary in approach yet can negatively contribute to issues requiring Hemispheric responses to threats like Transnational Organized Crime (TOC), disinformation challenges, and harmful economic activities. Nevertheless, the Hemisphere cannot create strategies designed to cease all ESA participation. Rather, a comprehensive understanding of where Hemispheric nations must press for better ESA behavior from countries such as Iran, Russia, and China while seeking new ways to increase integration of positive ESA influences to reduce the likelihood of traditional interstate conflicts will be key. All this while minimizing the effects of ever-present Multi-Dimensional Security (MDS) threats and challenges as global economic uncertainties persist that will likely have outsized, negative impacts on various regions of the world.