The solid tumor microenvironment (TME) is a complex network of cancer, stromal, and immune cells, along with signal molecules and extracellular components. It plays a crucial role in tumor progression and resistance to immunotherapies. mRNA-based approaches offer new possibilities to modify these processes in a controlled manner. In collaboration with clinical partners in Heidelberg, Mainz, and Essen, we will analyze tumor biopsies from colorectal and pancreatic cancer patients. Multi-omics approaches, including genome, transcriptome, and proteome analyses, will be integrated using AI-based bioinformatics to characterize the TME in detail. Leveraging mRNA-lipid nanoparticle technology, we will modulate the TME ex vivo and test different combinations of signal molecules such as cytokines and chemokines. Additionally, we will explore synergies with established immunotherapies like CAR-T and TCR-T cells. Our goal is to extensively characterize the TME and develop personalized strategies to enhance the immune response against tumors, ultimately improving cancer immunotherapy.