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The development of advanced feed spacers under different working conditions can enhance the performance of the reverse osmosis (RO) desalination process. The 3D-printed experimental results on triply periodic minimal surfaces (TPMS)-based spacers in previous literature indicate that the spacers have higher permeation flux of water compared to those of the common commercial spacers. In this paper, a hybrid modeling approach is developed and applied to predict and evaluate the performance of TPMS-based spacers. The effect of feed channels' height and porosity on the performance of spacers in brackish water RO (BWRO) process is studied by using a high-throughput approach. The predicted pressure drop by new simulations using the TPMS-based spacers (≈0.09–0.27 bar) from inlet to outlet in a typical two-stage BWRO system is reduced by more than 89% than that of using the commercial spacer (≈2.57 bar). Using the designed advanced spacers, the average permeation flux of water increases more than 8.6% compared to that of the commercial one. With the increase in feed channel height and porosity, the performance of spacers is gradually improved. TPMS-based spacers have significant industrial application prospects. [ABSTRACT FROM AUTHOR]