For every omics approach sample preparation is one of the most critical steps. Especially tissue sampling is very challenging because during the process of homogenization biomolecules are known to be converted by chemical reactions like oxidation as well as enzymatic reactions. The latter are caused by the release of enzymes from their compartments during homogenization. We have recently shown that sampling of tissues for proteomics with a picosecond infrared laser (PIRL) is very soft. Labile molecules like glycoproteins stay intact during laser ablation. Even enzymatic activities of proteins are maintained (1). Furthermore, the total yield of proteins with respect to their total number and total amount is significantly better compared to conventional homogenization. Proteoforms during tissue sampling with PIRL also remain intact in contrast to conventional homogenization (2). Thus, especially for the future of top-down proteomics PIRL is very promising (3). In addition to the application of PIRL for tissue sampling for proteomics, we performed a series of experiments applying infrared laser systems for tissue sampling for lipidomics and metabolomics. We sampled different pig brain areas with PIRL and investigated the condensates of the tissue aerosols with shot-gun lipidomics. By principle component analysis we were able to differentiate the different brain tissues. We compared the yields of metabolites obtained by conventional tissue sampling and by PIRL. The metabolites of both homogenization procedures were analyzed with p180-kit of Biocrates, by which approximately 180 metabolites are quantified via selected reaction monitoring by LC-MS and flow-injection analysis (FIA) by a triple quadrupole mass spectrometer. The results clearly showed that PIRL is more efficient in tissue sampling for proteomics. Furthermore, PIRL is giving access for volatile labile molecules by irradiation of tissues. In summary tissue sampling with PIRL for lipidomics, metabolomics and proteomics is advantageous compared to classical sampling and homogenization methods, giving higher yields of intact biomolecules and thereby allowing a closer and more realistic view to the original composition of biomolecules in intact tissues.