Single-cell sequencing (SCS) is a crucial tool to reveal the genetic and functional heterogeneity of tumors, providing unique insights into the clonal evolution, microenvironment, drug resistance, and metastatic progression of cancers. Microfluidics is a critical component of many SCS technologies and workflows, conferring advantages in throughput, economy, and automation. Here, we review the current landscape of microfluidic architectures and sequencing techniques for single-cell omics analysis and highlight how these have enabled recent applications in oncology research. We also discuss the challenges and the promise of microfluidics-based single-cell analysis in the future of precision oncology.