This study shows a very effective way to design thermosetting network compositions with biobased monomers by implementing a regime of structured experiments and analytics. The biobased content in a methacrylate resin was strategically increased by substituting compounds with sustainable alternative structures. The sustainable methacrylate monomers have been synthesized from the biobased diols by new routes presented in this work. With implementation of novel monomers, the change of composition in thermosetting resin materials significantly affects the network formation and mechanical properties. Investigating the influences of different monomer compounds on various properties was the base to understand later changes when including biobased monomers from sustainable resources. Therefore, a strategic analytical scheme was implemented, including reproducible reaction monitoring via near-infrared spectroscopy, differential scanning calorimetry, and rheology followed by material characterization. A model resin system of a two-component methacrylate resin as curing resin was studied using design-of-experiment to comprehend the influences of the components, i.e., base resin, cross-linker, and reactive thinner. The results show a strong dependence of the reaction progress on the cross-linker ratio in the system. Material properties such as thermal stability rely on the base resin ratio and structure. Comparison of the resins with biobased structures to the model resin system was used to assess their applicability, with the result that the chosen biobased components are very promising regarding the final cured resin properties.