Abstract The Ornithodoros moubata (Om) soft tick, a vector for diseases like tick‐borne human relapsing fever and African swine fever, poses challenges to conventional control methods. With diminishing insecticide efficacy, harnessing the tick's microbiota through innovative approaches like microbiota‐driven vaccination emerges as a promising strategy for sustainable and targeted disease control. This study investigated the intricate relationship between Pseudomonas , a keystone taxon in the Om microbiome, and its impact on tick fitness, microbiome structure and network dynamics. Utilizing in silico analyses and empirical vaccination experiments, the role of Pseudomonas within microbial networks in the tick midguts (MG) and salivary glands (SG) of Om was studied. Additionally, the consequences of anti‐microbiota vaccines targeting Pseudomonas and Lactobacillus on tick fitness, microbiome diversity and community assembly were explored. The result of the study shows that in Om, Pseudomonas plays a central role in microbial networks, influencing keystone species despite being categorized as peripheral (interacting with 47 different taxa, 13 of which are keystone species). Anti‐microbiota vaccination targeting Pseudomonas and Lactobacillus yields distinct effects on tick fitness, with Pseudomonas vaccination significantly impacting female tick survival, while Lactobacillus significantly reduced oviposition and fertility. Microbiome changes post‐vaccination reveal diversity alterations, emphasizing the impact of vaccine choice. Community assembly dynamics and network robustness analyses highlight Pseudomonas ' pivotal role, in influencing topological features and network resilience. The findings of the study provide comprehensive insights into the intricate dynamics of Om microbial networks and the potential of targeted microbiota‐driven vaccines for tick control.