Methane, the second most abundant greenhouse gas after carbon dioxide, represents a critical target in climate change mitigation efforts. Owing to their unique ability to utilize methane, methanotrophs have received substantial attention in greenhouse gas mitigation and low-carbon biomanufacturing, making the understanding of their metabolic pathways and ecological functions a vibrant research area worldwide. In recent years, the rapid development of high-throughput omics technologies and the integration of multi-omics analysis have accelerated a paradigm shift in methanotroph research, enabling the deep evolution from the identification of single gene functions to the elucidation of systemic metabolic processes. This review systematically summarizes the progress in the application of genomics, transcriptomics, proteomics, and metabolomics in methanotroph research, highlighting the decisive roles of omics technologies in elucidating carbon assimilation flux distribution in aerobic methanotrophs, uncovering novel metabolic pathways of anaerobic methane oxidation, and deciphering cross-domain interactions and electron transfer mechanisms within microbial consortia. To address current bottlenecks in the industrial application of methanotrophs, including poorly understood environmental adaptation mechanisms, imbalanced metabolic flux in chassis cells, and limited gas-liquid mass transfer efficiency, this review proposes a shift from descriptive omics toward function-driven and precision-intervention research. By integrating single-cell multi-omics and artificial intelligence-enhanced modeling, future studies may construct efficient artificial methanotrophic cell factories and synthetic microbial communities, thereby providing innovative biological solutions for achieving the global carbon neutrality goal.