Seawater instead of freshwater to produce concrete is an effective measure to save freshwater resources. However, the presence of harmful ions in seawater restricts its broader application. The incorporation of supplementary cementitious materials (SCMs) has the potential to significantly mitigate these adverse effects. Consequently, there is a growing interest in understanding the mechanisms by which SCMs function in seawater-mixed cementitious systems. In this study, a quadratic polynomial prediction model with the mechanical properties and dry shrinkage of the composite matrix as the response target was analyzed by the response surface method (RSM). Tests and analytical techniques elucidated the effects of metakaolin (MK) and ground granulated blast-furnace slag (GGBS) on the hydration process of the pastes after seawater mixing. The results revealed that the compressive strength and dry shrinkage were influenced by single-factor or multi-factor interactions. The optimal mix design (MK=20.2 % and GGBS=10.0 %) was experimentally validated, showing an absolute error of 1.5 %. The microstructural analysis indicated that MK and GGBS expedited essential pozzolanic reactions. Enhanced strength in mixtures before 3 d was attributed to cation exchange and initial flocculation. In the 28 d specimens, the increase in strength was related to the growth of Friedel’s salt crystals and C-(A)-S-H gels. Due to the presence of the C-(A)-S-H gels and AFm phases, chloride ions were efficiently immobilized, and the shrinkage of the matrix was reduced.