In recent decades, reported cases and geographic shifts of (re)emerging vector-borne diseases have been progressively increasing, due in part to rapid urbanization, changes in land use, globalization leading to increased trade and travel, and the changing global climate [1]. These factors are also increasing human exposure to animal reservoirs and arthropod vectors, including increased transmission of pathogens to naïve human populations [1,2]. Ticks transmit the highest number of pathogen species to vertebrates of any blood-feeding arthropod and are a growing threat to public health and agricultural systems worldwide [3,4].In the United States nearly 95% of reported vector-borne diseases are transmitted by ticks [5]. Of the almost 30 different identified tick-borne diseases in the Western Hemisphere, 12 are considered current and emerging threats to human health in the U.S. [5,6]. Lyme disease is the most frequently reported vector-borne disease in the U.S., with approximately 30,000 confirmed annual cases but upwards of 400,000 individuals that receive treatment for Lyme disease annually [7,8]. The continued expansion of the primary vector, Ixodes scapularis (blacklegged tick), into new habitats and geographic regions is concerning [9]. The future poses challenges to tick-borne disease management and predicting the challenges and mitigation strategies is difficult.One such challenge is climate change, which is implicated in current and future alterations to geographic ranges and population densities of several tick species of medical and veterinary importance [10]. High infestation burdens and associated mortalities due to Dermacentor albipictus (winter tick) on moose (Alces alces) and other cervids and the range expansion of I. scapularis are both partially attributed to the effects of climate change [11,12,13,14,15]. Warmer temperatures, particularly warmer winters, are hypothesized to be a leading factor associated with I. scapularis range expansions across eastern and central Canadian provinces [16]. Global climate change will affect tick biology and the hosts and reservoirs involved in tick-borne disease cycles [17,18]. Not only are the vectors and pathogens affected by climate change, but they are affected differentially leading to nonlinear responses and new relationships among vectors, pathogens, and hosts [19].In addition to transmitting disease-causing pathogens, ticks can also cause morbidity and mortality through painful bites, inflammation, increased stress, inducing tick paralysis and bite-associated meat allergies, toxicosis, or even exsanguination in animals [20]. High tick infestations have led to epizootics in certain ecosystems, with climate change-driven warmer, milder winters often implicated as a principal factor in increased tick overwintering survival [18]. “Ghost moose” have become a banner species for this increase in high parasite loads, with D. albipictus infestations on moose so severe that they can result in severe anemia, decreased fecundity in cows, and mortality [21,22].Another challenge is that modern technological advances have created an increasingly interconnected world. The speed and frequency of trade and travel have contributed to an increase in exotic and invasive tick species introductions [23,24]. The recently detected invasive species to the continental U.S., Haemaphysalis longicornis (longhorned tick), is another species with a propensity for high tick burdens on parasitized animals, particularly cattle, and is of medical and veterinary importance due to this aggregation behavior, capacity for parthenogenetic reproduction, and pathogen transmission potential [25,26,27,28]. The longhorned tick has been introduced and proliferated in numerous new regions worldwide and requires intensive surveillance as well as rapid identification and control measures [25,29,30,31,32].While not a new challenge, effective and consistent disease surveillance, control, and management strategies along shared geographic borders remain a critical challenge in managing ticks and tick-borne diseases, particularly with increased movement across borders due to globalization [23,33,34]. This movement is also fueled by increased meat and dairy consumption and higher demand for livestock trade, increasing the importance of management of transboundary animal diseases and their respective vector species [33,34]. For example, cattle fever ticks (Rhipicephalus spp.) are important endemic and invasive ectoparasites of cattle in numerous regions worldwide and can result in substantial welfare concerns and economic losses to the cattle industry [35]. Cattle fever ticks, vectors of the causative agents of bovine babesiosis, are endemic throughout many regions of Mexico [36,37]. This not only affects Mexico’s cattle herds but threatens the re-introduction and re-establishment of cattle fever ticks into the southern U.S. through cattle trade and the movement of wildlife alternate hosts across the Mexico–U.S. border [38,39,40]. This system exemplifies the challenges of implementing effective management and control strategies in disease systems that share common geography across international borders [33,41].The complex epidemiology and ecology associated with tick-borne diseases presents another challenge. Many tick species prefer one host species but will opportunistically feed on a variety of species, and many hard ticks require two to three different hosts to complete their life cycle [6]. This not only complicates which host species are affected, but also which pathogens may be acquired from these different hosts and transferred to other species by a given tick [10]. A One Health approach, which acknowledges the interconnected nature of human, animal, and environmental health and promotes collaborations between these sectors, is required to successfully manage vector-borne and zoonotic diseases [42,43,44]. This interdisciplinary approach will be paramount for successful tick control and tick-borne disease mitigation strategies and it is imperative for medical and veterinary professionals, policy-makers, and researchers to collaborate to better understand how tick-borne pathogens are moved in the environment and how they may manifest in disease in different host species [45] (Figure 1). While these efforts can be led by the scientific community, input and collaboration from scientists and non-scientists alike will be necessary to identify and implement effective long-term solutions.The objectives of this review are to (1) identify the major modern challenges to tick control and (2) develop best management strategies for tick control given these challenges. The following three conditions were identified as the primary challenges to tick control given our interconnected world: (1) global climate change, (2) globalization of trade and travel, and (3) permeable political borders. To further explore these conditions, three case studies from a U.S. borders perspective were used to highlight the challenges and recommendations for tick control in an interconnected world (Figure 2).