<p>Aquaculture has emerged as a cornerstone of global food production, yet infectious diseases continue to threaten its productivity and sustainability. In teleost fish, mucosal surfaces such as the skin, gills, gut, and nasopharynx serve as vital immune barriers and primary sites of host–pathogen interaction. This review synthesizes current understanding of the cellular and molecular mechanisms underpinning fish mucosal immunity, with emphasis on mucosa-associated lymphoid tissues (MALTs), including GALT, SALT, GIALT, and NALT. It highlights the pivotal role of immunoglobulin T (IgT) as a functional analogue of mammalian IgA and its interplay with resident microbiota in maintaining mucosal homeostasis. Advances in functional feeds, probiotics, and immunostimulants are discussed as promising strategies to enhance mucosal resilience. Particular attention is given to the development of mucosal vaccines and adjuvants, exploring diverse delivery routes—immersion, oral, and nasal, and the molecular pathways, including Toll- and NOD-like receptor signaling, that modulate immune activation. Emerging technologies such as single-cell transcriptomics, immunoinformatics, and microbiome–transcriptome integration are reshaping our capacity to characterize mucosal responses and design precision vaccines. Despite these advances, challenges remain in antigen stability, regulatory approval, and the establishment of correlates of mucosal protection. Addressing these gaps through species-specific, microbiota-informed vaccine design and integrative immunological approaches will be crucial for advancing disease management and promoting sustainable aquaculture.</p>