Ticks are obligatory hematophagous parasites that serve as vectors for a large amount of important human and livestock pathogens around the world, and their distribution and incidence of tick-associated diseases are currently increasing because of environmental biomass being modified by both climate change and other human activities. Hyalomma species are of major concern for public health, due to their important role as vectors of several diseases such as the Crimea–Congo hemorrhagic fever (CCHF) virus in humans or theileriosis in cattle. Characterizing the Hyalomma-associated microbiota and delving into the complex interactions between ticks and their bacterial endosymbionts for host survival, development, and pathogen transmission are fundamental, as it may provide new insights and spawn new paradigms to control tick-borne diseases. Francisella-like endosymbionts (FLEs) have recently gained importance, not only as a consequence of the public health concerns of the highly transmissible Francisella tularensis, but for the essential role of FLEs in tick homeostasis. In this comprehensive review, we discuss the growing importance of ticks associated with the genus Hyalomma, their associated tick-borne human and animal diseases in the era of climate change, as well as the role of the microbiome and the FLE in their ecology. We compile current evidence from around the world on FLEs in Hyalomma species and examine the impact of new molecular techniques in the study of tick microbiomes (both in research and in clinical practice). Lastly, we also discuss different endosymbiont-directed strategies for the control of tick populations and tick-borne diseases, providing insights into new evidence-based opportunities for the future.