The present disclosure includes systems, methods, and non-transitory computer readable media that utilize a genetic framework to generate enhanced digital layouts from digital content fragments. In particular, in one or more embodiments, the disclosed systems iteratively generate a layout chromosome of digital content fragments, determine a fitness level of the layout chromosome, and mutate the layout chromosome until converging to an improved fitness level. The disclosed systems can efficiently utilize computing resources to generate a digital layout from a layout chromosome that is optimized to specified platforms, distribution audiences, and target optimization goals.