Due to the misuse of hormones and antibiotics resulting in drug residues in meat products, serious concerns have arisen regarding to the potential risks for human health. In this paper, a simple and efficient method was developed to simultaneously quantify six steroid hormones and six antibiotics in fatty foods by combining pressurized liquid extraction (PLE) with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Adsorbents, extraction temperature, extraction time, recycle time and several other parameters were optimized in current investigation. The optimized PLE method was employed by using n-hexane-methanol-acetonitrile (2:1:1, v/v/v) as extraction solvent, silica gel as lipid sorbent, and the optimum parameters were 60 °C, 1500 psi and 10 min, respectively. Under the optimal conditions, the recoveries of spiked samples ranged from 82.2% to 115.0%. The limits of quantifications (LODs) were from 0.4 to 25.0 μg/kg. The developed PLE method was successfully applied to analyze steroid hormones and antibiotics in 27 fatty foods of hotpot ingredients without any additional clean-up steps. The results showed that the residues of estradiol benzoate (EB) and enrofloxacin (EN) in some matrices were much higher than maximum residue limits (MRLs) value, especially EB in fish, which exceeded 176.7 μg/kg. The results demonstrated that the developed method was sensitive and efficient in testing hotpot ingredients, and was an excellent analytical tool for monitoring residues of steroid hormones and antibiotics in fatty foods.