Abstract: Single-cell multimodal omics technologies have emerged as a revolutionary approach in the life sciences, overcoming the limitations of traditional bulk-cell studies and single-modal omics focusing on isolated analyses. These cutting-edge techniques enable simultaneous interrogation of multiple molecular layers-including genome, transcriptome, epigenome, and proteome-at single-cell resolution. This review provides a comprehensive overview of the fundamental principles, methodological features, and broad biomedical applications of single-cell multimodal omics. We first introduce the basic concepts of these technologies, followed by detailed explanations of key technical principles underlying genome-transcriptome co-profiling, epigenome-transcriptome joint sequencing, and proteome-transcriptome integrated analysis. Furthermore, we explore their applications across diverse fields such as tumor heterogeneity studies, developmental biology, neuroscience research, and precision medicine, while also discussing current technical challenges and future directions.