Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI), an ambient, commercially available MSI technique , presents a promising alternative for single-cell metabolomics. DESI-MS involves charged solvent droplets impacting a sample's surface to desorb molecules and generate analytes' ions for direct MS detection. DESI-MSI combines the benefits of minimal sample preparation with the capability to ionize a wide range of metabolites directly from the sample surface with little or no sample preparation. In addition, DESI does not require the application of matrix molecules, minimizing the interfering ions and simplifying data interpretation. As a commercialized technique, DESI offers a more robust and user-friendly setup, facilitating broader application.