High-throughput (HT) methodologies are extensively applied in synthetic biology for the rapid enrichment and selection of desired properties from a wide range of genetic diversity. In order to effectively analyze these vast variants, HT tools must offer parallel experiments and compact reaction capabilities to enhance overall throughput. Here, we discuss about various aspects of three representative high-throughput screening (HTS) systems: microwell-, droplet-, and single-cell-based screening. These systems can be categorized based on their reaction volume, which in turn determines the associated technology, machinery, and supporting applica-tions. Furthermore, HT techniques that rapidly connect numerous genotypes and phenotypes have evolved to enhance the precision of predictions through the integra-tion of digital technologies like machine learning and artificial intelligence. The use of advanced HT techniques within bio-foundry will enable rapid selection and analysis from exten-sive genetic diversity, making it a driving force for the advancement of synthetic biology.