<p>Nowadays, the abuse of synthetic cannabinoids has aroused the world’s great attention. However, the determination&#xa0;of synthetic cannabinoids in wastewater faces the bottleneck of complex species and very low content. Therefore, this work integrated GO-Fe₃O₄ with an ionic liquid (ILs-GO-Fe₃O₄) to create a mixed hemimicelles magnetic solid-phase extraction (MHMSPE) system for the detection of synthetic cannabinoids (SCs) in wastewater samples using ultrahigh-performance liquid chromatography—tandem mass spectrometry (UHPLC-MS/MS). Because of the multiple interaction sites of mixed hemimicelles’ magnetic solid-phase extraction materials, multi-structural synthetic cannabinoids can be enriched simultaneously. Under the optimized conditions, the limits of quantitation (LOQ) of the method were as low as 10–50&#xa0;pg/L, lower than other methods. The average recoveries of 18 analytes were in the range 71.23–96.08% with relative standard deviations (RSD) lower than 15% (<i>n</i> = 6). To our knowledge, this is the first development of magnetic solid-phase extraction for large-volume samples pretreatment (1 L) and ultra-high sensitive detection of synthetic cannabinoids (10&#xa0;pg/L), due to the high enrichment factor (10,000-fold). The extraction process was convenient, accurate, and rapid, and offers significant potential for ultra-high sensitivity detection in large-volume samples, providing a valuable tool for simultaneous broad-spectrum extraction and drug abuse monitoring.</p> Graphical abstract <p></p>