The chapter discusses the advancements in single-cell omics and multiomics for high-resolution molecular profiling. Single-cell omics technologies have revolutionized molecular profiling by providing detailed insights into cellular heterogeneity and complexity, allowing the analysis of individual cells and revealing diverse cell types, dynamic states, and rare populations. Traditional bulk omics methods average signals from heterogeneous cell populations, obscuring important cellular nuances. Single-cell omics studies offer unprecedented resolution and sensitivity, enabling researchers to unravel the molecular landscape of individual cells. The integration of multimodal omics data within a single cell provides a comprehensive view of cellular processes. By combining multiple omics dimensions, multimodal omics approaches facilitate the elucidation of complex cellular interactions, regulatory networks, and molecular mechanisms. This integrative approach enhances our understanding of cellular systems, from development to disease. The chapter covers the principles and methodologies of single-cell and multimodal omics, highlighting the strengths and limitations of different techniques. It also presents case studies demonstrating the applications of single-cell and multimodal omics in various fields, including developmental biology, neurobiology, cancer research, immunology, and precision medicine. Key topics include single-cell isolation and barcoding, genome, transcriptome, proteome, methylome, chromatin accessibility, and chromatin conformation capture. The chapter discusses the challenges and opportunities in the field, emerging technologies, and future directions in single-cell and multimodal omics research. It emphasizes the importance of long-read sequencing technologies in overcoming the limitations of short-read sequencing and the potential of multiomics approaches in capturing and characterizing all molecules within a cell.The chapter discusses the advancements in single-cell omics and multiomics for high-resolution molecular profiling. Single-cell omics technologies have revolutionized molecular profiling by providing detailed insights into cellular heterogeneity and complexity, allowing the analysis of individual cells and revealing diverse cell types, dynamic states, and rare populations. Traditional bulk omics methods average signals from heterogeneous cell populations, obscuring important cellular nuances. Single-cell omics studies offer unprecedented resolution and sensitivity, enabling researchers to unravel the molecular landscape of individual cells. The integration of multimodal omics data within a single cell provides a comprehensive view of cellular processes. By combining multiple omics dimensions, multimodal omics approaches facilitate the elucidation of complex cellular interactions, regulatory networks, and molecular mechanisms. This integrative approach enhances our understanding of cellular systems, from development to disease. The chapter covers the principles and methodologies of single-cell and multimodal omics, highlighting the strengths and limitations of different techniques. It also presents case studies demonstrating the applications of single-cell and multimodal omics in various fields, including developmental biology, neurobiology, cancer research, immunology, and precision medicine. Key topics include single-cell isolation and barcoding, genome, transcriptome, proteome, methylome, chromatin accessibility, and chromatin conformation capture. The chapter discusses the challenges and opportunities in the field, emerging technologies, and future directions in single-cell and multimodal omics research. It emphasizes the importance of long-read sequencing technologies in overcoming the limitations of short-read sequencing and the potential of multiomics approaches in capturing and characterizing all molecules within a cell.