Tick-borne diseases cause in enormous burden on human, livestock, and wildlife health globally and are driven by the increasing abundance and geographic expansion of medically important tick species. More recently, tick-borne disease emergence is occurring in urban landscapes due to complex feedbacks between the environment, humans, wildlife, and ticks. In this dissertation, I focus on the ecological conditions that allow for tick-borne disease emergence in a city. I use a combination of spatial landscape modeling, empirical data collection, wildlife movement tracking to determine drivers of zoonotic hazards in New York City, NY, and employ vector genomics to examine vector dispersal in the northeastern United States. In chapter one, I pair tick collection throughout the five boroughs of New York City with landscape connectivity modeling to examine how green space connectivity and habitat availability affects the density and infection of questing nymphs – an important epidemiological measure of human risk for tick-borne diseases. I found that green spaces that were highly connected for deer had higher nymph density and infection prevalence for Borrelia burgdorferi sensu stricto, the etiologic agent of Lyme disease. In chapter two, I use camera trapping, live trapping, and tick collection on Staten Island, NY, to examine how landscape fragmentation – through changing habitat size and connectivity – shapes the host community available for questing Ixodes scapularis nymphs. Further, I examined whether patterns in host species abundance and activity correlate with the density of nymphs and their infection prevalence with three different pathogens that vary in host-specificity, B. burgdorferi, Babesia microti, and Anaplasma phagocytophilum. I found associations between host species and the size and connectivity of the park habitat, identified host species which amplified and removed ticks in the environment, and determined links between host activity and abundance and the infection prevalence of nymphs with host-specific pathogens. In chapter three, I utilize movement data from 59 white-tailed deer on Staten Island, NY, to assess the drivers of movement and its impact on tick-borne disease hazard across the landscape. I found that white-tailed deer avoid anthropogenic development at fine spatial scales when establishing home ranges but select for anthropogenic resources within their home range, increasing the potential to distribute ticks into environments that interface with humans. Finally in chapter four, I use double digest Restriction Associated DNA sequencing to examine the genetic differentiation of six I. scapularis populations across the Northeast region. I found high levels of gene flow across a spatial scale of 400 km, likely resulting from frequent host-mediated dispersal events combined with large I. scapularis populations. Taken together, this work emphasizes that host movement and ecology are critical determinants of urban tick-borne disease emergence through directing vector and pathogen dispersal, serving as pathogen reservoirs in urban habitats, and interfacing with humans in unique ways that increase human exposure to zoonotic hazards.