Humans face a grand challenge as growing demands on the environment for resources to provide for an ever-expanding population threaten the existence of wildlife populations, degrade land, and pollute air and water. Public investment and policy decisions that will shape future interactions of humans, animals and the environment require scientific input to help find common ground for durable and sustainable success. iCOMOS-2016 brought together more than 350 scientists, regulatory authorities, health experts, and student trainees from 32 countries to inform and discuss the impacts of air quality on health and economics, the complexities of water – quality, access, international conflicts, uses, the burgeoning opportunities and uncertainties in precision medicine that can provide novel solutions to emerging health threats, and the role of science and science communication in health policy formulation. Workshops focused on the resources and tools available to deliver the knowledge that is needed for addressing complex health challenges. Topics included (i) the key roles of physician-scientists and multidisciplinary teams; (ii) big data tools for analysis and visualization; (iii) international policy development processes; and (iv) health models that benefit animals and humans. Key insights gained from oral and poster presentations, panel discussions, workshops and networking were that local and regional health challenges at the interface of humans, animals and the environment are all variations of the same overarching conflicts, and that international gatherings provide new opportunities for investigation and policy development that are broadly applicable. Already, future annual meetings beginning in 2018 are scheduled to be held in the U.S., Thailand, Chile, Turkey.