Harmful substances in consumer goods pose serious hazards to human health and the environment. However, due to the vast variety of consumer goods and the complexity of their substrates, it is difficult to simultaneously detect multiple harmful substances in different materials. This paper presents a method for the simultaneous determination of 41 harmful substances comprising 17 phthalates (PAEs), 8 organophosphate flame retardants (OPFRs), and 16 polycyclic aromatic hydrocarbons (PAHs) in five types of products using the matrix-matching calibration strategy. The method employs an efficient ultrasonic extraction procedure using a mixture of dichloromethane and methylbenzene, followed by dissolution–precipitation and analysis through gas chromatography–mass spectrometry. Compared with previous experiments, we established a universal pretreatment method suitable for multi-matrix materials to simultaneously determine multiple harmful substances. To evaluate the effects of the matrix on the experimental results, we compared neat standard solutions and matrix-matching standard solutions. The results demonstrated that all compounds were successfully separated within 30 min with excellent separation efficiency. Additionally, the linear relationships of all analytes showed strong correlation coefficients (R2) of at least 0.995, ranging from 0.02 mg/L to 20 mg/L. The average recoveries of the target compounds (spiked at three concentration levels) were between 73.6 and 124.1%, with a relative standard deviation (n = 6) varying from 1.2% to 9.9%. Finally, we tested 40 different materials from consumer products and detected 16 harmful substances in 31 samples. Overall, this method is simple and accurate, and it can be used to simultaneously determine multiple types of hazardous substances in multi-matrix materials by minimizing matrix effects, making it an invaluable tool for ensuring product safety and protecting public health.