This paper explores fundamental mechanisms of negatively thermodynamic toughening during microphase separations of double network (DN) hydrogels, which have dynamically coordinating components with adjustable swelling behavior and designable multi-shape memory effect (multi-SME). Based on the Flory-Huggins theory and Fick’s second law, a thermodynamic model is formulated to study the diffusive dynamics, cooling-triggered multi-SME and mechanical toughness of the DN hydrogels. The negatively thermodynamic toughening effect of the DN hydrogels is strongly dependent on their water concentration, hydrophobic transition, and microphase separation. Finally, effectiveness of this new model is demonstrated by applying it to predict dual-SME, quadruple-SME and thermodynamic shape memory behaviors of DN hydrogels. This study provides a methodology for the design of shape memory DN hydrogels with tunable, giant and programmable cooling-triggered SME.