Cultivation of Saccharina latissima, a brown macroalga, is fast developing in Europe and North America for the sustainable production of food and biorefinery materials and important ecosystem services. Prior studies have demonstrated large spatial variability in the yield and chemical composition of the cultivated S. latissima, even within a small coastal bay. Using a validated hydrodynamic-biogeochemical-kelp model, this study examined main drivers of the spatial variability in S. latissima growth dynamics in 40 hypothetical farms throughout a Dutch coastal bay, the Eastern Scheldt. Results indicate that temperature plays a primary role in driving the spatial variability. For example, S. latissima yield in the deeper and better flushed western part is more than double that in the eastern part, mainly due to its 2–3°C warmer seawater in winter. It is also found that S. latissima benefits from co-cultivation with shellfish, since nutrients excreted by shellfish replenish its nitrogen reserve, which fuels a relatively high growth rate in the nitrogen-depleted late spring. The model assessment offers insight into optimal potential locations of S. latissima farms in the Eastern Scheldt. Applicability of our modelling approach to other coastal ecosystems and possible further improvements for assisting in seaweed farming practice are discussed.