Single‐Cell and Spatial Omics: Methods and Applications

ABSTRACT Single‐cell and spatial omics have revolutionized biomedical research by enabling high‐resolution molecular profiling across cells and tissues, thereby overcoming key limitations of bulk sequencing and revealing unprecedented cellular heterogeneity and spatial organization central to development, homeostasis, and disease. Specifically, advances in high‐throughput, subcellular, and multiomics profiling are promoting the field toward deeper insights. In parallel, computational progress, including generative artificial intelligence (AI) and foundation models, is developing rapidly for manipulating multimodal multiomics data. These advancements have been applied to diverse diseases and biological systems, facilitating innovative biomedical findings. However, a significant gap persists between rapid methodological advances and their systematic application for deciphering human biology and pathology. This review synthesizes recent breakthroughs in single‐cell and spatial technologies and surveys computational methods, including AI‐driven approaches, foundation models, and multi‐omics integration algorithms for both single‐cell and spatial analyses. We then summarize representative applications across major human organ systems in health and disease, highlighting opportunities for biomarker discovery, therapeutic target identification, and precision medicine. Finally, we discuss current challenges and future directions for bridging technological innovation with robust biomedical discovery and translational impact. This review provides a vital guide for researchers in the field, offering critical insights for accelerating the translation of single‐cell and spatial omics.