Understanding complex tick-borne pathogen systems and responding to the urgent human health threat requires coordinated multidisciplinary research and management efforts across broad geographic areas and over long time periods. Hosts, vectors, and pathogens in the system interact and simultaneously respond to dynamic environmental conditions. Ongoing and planned large-scale white-tailed deer (Odocoileus virginianus) monitoring and culling to restore forest understory communities across multiple national parks (Bates 2009) provides an opportunity to test how ecological-community-scale interventions (deer culling) can directly and indirectly influence ticks and pathogens and thus reduce human disease risk. Deer are important hosts for ticks, and as a keystone forest species, deer also have cascading effects on ticks through impacts to forest structure and composition that provide habitat to hosts and vectors. Here we propose that implementation of hybrid-capture next-generation sequencing technology will enable comprehensive detection and characterization of pathogens in ticks and host blood meals over time. As an added benefit we will be able to measure the effects of management efforts on: 1) the occurrence of specific tick-borne pathogens, 2) coinfection potential, and 3) the development of novel tick-borne pathogens, and 4) the tick bloodmeal sources. This research will implement a pathogen detection and subtyping workflow that is scalable for use in monitoring the burden and evolution of vector-borne diseases that impact human and wildlife health.