Food safety and quality have been gaining increasing attention in recent years. Gas chromatography coupled to tandem mass spectrometry (GC–MS/MS), a highly sensitive technique, is gradually being preferred to GC–MS in food safety laboratories since it provides a greater degree of separation on contaminants. In the analysis of food contaminants, sample preparation steps are crucial. The extraction of multiple target analytes simultaneously has become a new trend. Thus, multi-residue analytical methods, such as QuEChERs and adsorption extraction, are fast, simple, cheap, effective, robust, and safe. The number of microorganic contaminants has been increasing worldwide in recent years and are considered contaminants of emerging concern. High separation in MS/MS might be, in certain cases, favored to sample preparation selectivity. The ideal sample extraction procedure and purification method should take into account the contaminants of interest. Moreover, these methods should cooperate with high-resolution MS, and other sensitive full scan MSs that can produce a more comprehensive detection of contaminants in foods. In this review, we discuss the most recent trends in preparation methods for highly effective detection and analysis of food contaminants, which can be considered tools in the control of food quality and safety.