The mucosal system serves as the primary barrier against respiratory diseases and plays a crucial role in combating viral infections through mucosal immunity. The resident microbial community constitutes the main component of the mucosal system and exerts a significant inhibitory impact on the invasion of exogenous agents. However, the precise relationship between resident microbiota, mucosal immunity, and viral infections remains incomplete. This review aims to summarize the regulatory interactions between the resident microbiota of the mucosal system and innate immune components such as mucosal immunity and trained immunity. By clarifying these complex relationships, this review seeks to identify potential targets for augmenting respiratory disease prevention strategies and developing novel vaccine formulations. Furthermore, we propose the possibility of integrating the fields of microbiome-based therapeutics and vaccine development to create multifunctional vaccine formulations capable of targeting mucosal immunity induction. Such an approach holds great potential in offering novel pathways and strategies for the prevention and treatment of respiratory diseases.