Severe asthma, characterized as a complex and heterogeneous chronic inflammatory disease, has witnessed significant advancements in biomarker research alongside a deepening understanding of its pathogenesis in recent years. These advancements have markedly improved diagnostic and therapeutic strategies for this condition. Each biomarker contributes uniquely to precision medicine in severe asthma by providing critical insights into its molecular underpinnings. This review synthesizes the latest global research progress on existing and emerging omics-based biomarkers that hold promise for refining the management of severe asthma. These biomarkers rapidly elucidate disease-specific pathophysiological pathways, thereby offering robust evidence to guide precision diagnosis and tailored therapeutic approaches. Furthermore, we highlight future directions in biomarker discovery, emphasizing their potential to overcome current limitations in phenotyping and therapeutic resistance.