The hybridisation of forward osmosis (FO) and membrane distillation (MD) has the potential to offer a solution to the increasing worldwide demand for clean water. However, accurate prediction of system behaviour, balancing of water transfer rates and the implementation of a suitable draw solution are needed to maximise permeate production. Currently, there is a lack of comprehensive mathematical tools available and further draw solution developments are required. In this study, an experimentally validated mathematical model was developed to simulate the FO-MD system. Draw solutes including sodium chloride (NaCl), tetraethylammonium bromide (TEAB) and polydiallyldimethylammonium chloride (PDAC), were used to characterise individual FO and MD permeate fluxes. The FO-MD system was then run using 0.5 M NaCl, TEAB and PDAC. The results showed that fouling was more significant in FO, and water transfer rate imbalances were identified in all systems. The experimental results and model were used to predict MD feed temperature and cross-flow velocity adjustments to achieve system water balance for each draw solution. As a result of this balancing, permeate production using NaCl, TEAB and PDAC was enhanced. This study suggests that the FO-MD system is a promising candidate for water purification when system performance is optimised through mathematical modelling.