The Community Engagement Core (CEC) within the Southwest Environmental Health Sciences Center (SWEHSC) is integral to developing and maintaining the relationships that allow SWEHSC to meet its mission of determining the human health impacts of environmental exposures among underserved populations in arid environments experiencing climate change. The CEC addresses structural environmental inequalities by facilitating multidirectional and culturally-anchored engagement between SWEHSC researchers, the National Institute of Environmental Health Sciences, and Southwestern educators, public health professionals, community members, and policy makers. The SWEHSC is in the arid Southwest, a region that is home to high proportions of Indigenous, Latinx, and rural communities living in understudied environmental conditions that include exposures to unique toxicants. Primary health concerns in these communities include cancer, diabetes, autoimmune diseases, reproductive disorders, and respiratory disease that can result from exposures to extreme heat, airborne pollutants, pesticides, forest fire smoke, dust storms, and drinking water contaminants such as per- and polyfluoroalkyl substances and arsenic. The CEC vision is to combine respect for Indigenous science, traditional ecological knowledge, “funds of knowledge,” and citizen observation/inquiry with modern scientific advances to engage Indigenous, Latinx, and rural communities and to design materials and programs to work towards environmental justice for these communities. The CEC applies this vision through four aims: 1) using multi-directional communication strategies to assure that SWEHSC investigators address the environmental health (EH) issues of greatest concern impacting our target communities; 2) ensuring the dissemination of key research findings to our target communities so that they may better protect their health; 3) evaluating the effectiveness of our risk and safety communication and report-back strategies to ensure that these communications effectively promote public health; and 4) assuring self-determination by training the next generation of EH scientists from these communities. In realizing these aims, the CEC equips the next generation of EH scientists with the necessary engagement skills and scientific knowledge to address structural environmental inequalities affecting the desert Southwest populations and to achieve sustainable EH justice.