There are great opportunities for innovation in the drug discovery process, particularly in the lead development phase. The traditional “design–synthesize–screen” cycle has seen little innovation as a whole despite major advances at each stage, including automated purification and synthesis as well as high throughput biological screening. It could be argued that the hit-to-lead and lead optimization processes remain slow and modular with inefficient flow of information, resulting in a loss of time and money. New flow technologies may provide a promising foundation for developing a continuous integrated small molecule optimization platform that would greatly enhance hit-to-lead and lead optimization programs. Herein, we discuss major developments in integrating synthesis, purification, screening, and machine learning into a single continuous-flow platform and provide some insight into future directions of this field.