The complex, bidirectional communication between the gut and the lungs, known as the “gut-lung axis,” profoundly influences host immune homeostasis and the pathogenesis of respiratory diseases. In recent years, multi-omics approaches, including metagenomics, metabolomics, and metatranscriptomics, have emerged as the core driving force for unraveling the complexity of this interorgan cross talk network. This review aims to systematically summarize the current omics-based evidence in the field of the gut-lung axis. We highlight key communication mechanisms discovered through multi-omics integration, particularly how gut microbiota-derived metabolites, exemplified by short-chain fatty acids (SCFAs), mediate distal immune regulation. Concurrently, we consolidate omics evidence from the contexts of respiratory infectious diseases, chronic lung disorders, and aging, systematically delineating the impact of gut dysbiosis on pulmonary pathophysiology via the gut-lung axis and emphasizing the feasibility of disease management in patients with lung diseases by modulating the gut microbiota. Although omics technologies have significantly advanced our understanding of this field, the challenge of effectively integrating vast, heterogeneous data and transitioning from “correlation” to “causation” remains a primary hurdle. By reviewing and discussing the current omics evidence in the gut-lung axis, this paper aims to provide new perspectives for future mechanistic explorations and clinical translation strategies.