<p>Tick-borne diseases represent a growing public health concern worldwide, yet the microbial factors that govern pathogen transmission remain incompletely understood. Over the past decade, high-throughput metagenomics and functional studies have revealed that two distinct microbial communities—the vertebrate host’s skin microbiota and the tick’s own microbiome—act synergistically as key modulators of pathogen acquisition, persistence within the vector, and successful transmission to the vertebrate host. At the feeding site, the skin microbiota orchestrates local cutaneous immunity, influences inflammatory responses, and can either hinder or inadvertently facilitate dermal establishment of tick-borne pathogens such as <i>Borrelia burgdorferi</i> sensu lato (s.l.), <i>Anaplasma phagocytophilum</i>, <i>Rickettsia</i> species, <i>Babesia</i> spp., and tick-borne encephalitis virus. Tick feeding itself induces rapid and sometimes long-lasting dysbiosis of the skin microbial community, creating temporal windows of vulnerability for pathogen invasion. Concurrently, within the tick vector, a core set of endosymbiotic bacteria, including <i>Rickettsia buchneri</i>, <i>Midichloria mitochondrii</i>, <i>Coxiella</i>-like, and <i>Francisella</i>-like endosymbionts, engage in complex mutualistic, competitive, and facilitative interactions. These symbionts regulate vector competence through nutrient provisioning (especially B-vitamins), direct competition for niche space, and immune priming or suppression of the tick’s innate immune system. Such interactions ultimately determine the maintenance, abundance, and transmissibility of tick-borne pathogens. By integrating these dual host–vector microbiome perspectives in a comprehensive review, we highlight emerging mechanistic insights into transmission ecology and biologically grounded targets for the prevention and control of tick-borne diseases, including anti-microbiota vaccines and paratransgenic and microbiome-based approaches.</p> Graphical Abstract <p></p>