<p>Building synthetic versions of biological cells from the bottom up offers an unprecedented opportunity to understand the rules of life and harness cellular capabilities in biotechnology. Whereas substantial progress has been made in recapitulating elementary cell functions, we argue that accelerating the engineering of synthetic cells requires a shift in research practices. The dominant approach—rationally designing and integrating functional modules—becomes restrictive when dealing with the massively complex biochemical pathways associated with life, especially when design principles remain unclear. We advocate moving away from theoretical rational design towards a data-driven model that is centred on library generation. Inspired by a systems chemistry perspective, this strategy prioritizes the systematic creation and distribution of composition–function libraries. To enable this, experimental strategies must integrate high-throughput synthetic cell generation, automation and closed-feedback control of workflows. Broad adoption will also require greater emphasis on quantitative benchmarking, and the de-skilling of techniques, supporting effective laboratory-to-laboratory collaboration.</p><p></p>