Molecular ferroelectrics have been widely adopted as alternatives to traditional ceramic and polymer ferroelectrics due to their outstanding piezoelectric and ferroelectric properties, as well as their unique advantages of flexibility and low acoustic impedance, among others. However, rationally designing and optimizing molecular ferroelectrics with high performance remain a significant challenge. This review gives a brief introduction on the very recent approaches for the targeted design of molecular ferroelectrics through H/F substitution. H/F substitution comes into being the guidelines for designing and optimizing molecular ferroelectrics as well as the blueprint for the discovery of new functionalities for practical applications. Finally, a perspective view of future research on the H/F-substituted molecular ferroelectrics is provided.