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Modern molecular analytical technologies in the “omics” arena plays a increasingly important role in clinical diagnostics. Technological advances have increased methodological sensitivity, allowing researchers to acquire detailed molecular information of smaller and smaller samples. The biggest challenge is to put that concerted information in the context of the biological problem the samples originate from. Innovative molecular imaging technologies at the single cell level, have impacted translational clinical research and beyond. Sensitive and selective molecular microscopes in modern spatial biology offer new insights in spatial and molecular complexity of cellular metabolism that contextualize cellular function in health and disease. Innovations in mass spectrometry based chemical microscopes have now firmly established themselves in translational molecular research. One key aspect of translational success is the ability to obtain this molecular information on thousands of molecules on a process relevant time- and length scale. Targeted and untargeted imaging technologies now offer new insights in the complexity that can be employed for systems medicine. The application of mass-tagged antibodies has enabled MALDI-MSI based immunohistochemistry to complement untargeted lipidomics and proteomics MSI. New strategies to integrate complex studies with spatial transcriptomics are rapidly gaining traction. In that context, single cells can now be analyzed in great molecular detail and in the context of their native tissue. Combined, this offers a true multi-omics approach that reveals contextual molecular complexity for patient stratification and personalized medicine.