Biological systems are inherently complex and heterogeneous. Deciphering this complexity increasingly relies on high-throughput single-cell omics methods and tools that efficiently probe the cellular phenotype and genotype. Here, we present a versatile technology based on semipermeable capsules (SPCs) tailored for a variety of high-throughput nucleic acid assays, including single-cell genome and mRNA sequencing, and fluorescence-activated cell sorting–based isolation of individual transcriptomes based on a nucleic acid marker of interest. Being biocompatible, the SPCs support single-cell cultivation and clonal expansion over long periods of time, thereby overcoming a fundamental limitation of droplet microfluidics platforms. Overall, the SPCs represent a customizable and broadly applicable tool for easy-to-use, scalable single-cell omics applications that are built on multistep biochemical reactions.