In food analysis, a trend towards on-site testing of quality and safety parameters is emerging. So far, on-site testing has been mainly explored by miniaturized optical spectroscopy and ligand-binding assay approaches such as lateral flow immunoassays and biosensors. However, for the analysis of multiple parameters at regulatory levels, mass spectrometry (MS) is the method of choice in food testing laboratories. Thanks to recent developments in ambient ionization and upcoming miniaturization of mass analyzers, (trans)portable mass spectrometry may be added to the toolkit for on-site testing and eventually compete with multiplex immunoassays in mixture analysis. In this study, we preliminary evaluated a selection of recent ambient ionization techniques for their potential in simplified testing of selected food contaminants such as pesticides, veterinary drugs, and natural toxins, aiming for a minimum in sample preparation while maintaining acceptable sensitivity and robustness. Matrix-assisted inlet ionization (MAI), handheld desorption atmospheric pressure chemical ionization (DAPCI), transmission-mode direct analysis in real time (TM-DART), and coated blade spray (CBS) were coupled to both benchtop Orbitrap and compact quadrupole single-stage mass analyzers, while CBS was also briefly studied on a benchtop triple-quadrupole MS. From the results, it can be concluded that for solid and liquid sample transmission configurations provide the highest sensitivity while upon addition of a stationary phase, such as in CBS, even low μg/L levels in urine samples can be achieved provided the additional selectivity of tandem mass spectrometry is exploited.