Designing efficient and green approaches to complex molecules is a challenge faced by any organization seeking to deliver modern pharmaceutical compounds to patients. The outcome of any route design effort, in terms of efficiency, is largely governed by the disconnections and synthetic strategies generated during the process of route scouting, coupled with the decisions made by the individuals responsible for the research. In this article, we delineate an approach, based on historical data, capable of quantifying the probable efficiency of a proposed synthesis prior to any research being conducted. This decision-making strategy can be used to both aid the decision-making process of innovators and to benchmark the outcome performance of the developed process, improving the efficiency of any manufacturing process developed. Through improved decision making and benchmarking, this approach could minimize the environmental impact of pharmaceutical production.