The instability of mRNA−lipid nanoparticles (LNPs) necessitates ultra-cold storage, limiting global distribution and their broader application in advanced delivery systems. Solid-state, water-free formulations enhance thermostability and enable integration into emerging delivery modalities such as microneedle patches. Previous efforts to stabilize mRNA−LNPs have been constrained by narrow formulation scope and low-throughput screening methods. Here we introduce Algorithm-Guided Experimental desi