Herein, a method for the multi-response optimization of a green and efficient solid phase extraction (SPE) sample treatment using non-modified multi-walled carbon nanotubes combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the quantification of ten heterocyclic aromatic amines (HAAs) in river and reservoir surface water samples. The proposed methodology was evaluated by employing experimental designs, which made the approach green. Ultra-trace amounts of HAAs were retained in the SPE cartridge. Then, the analytes were removed from the carbon nanotubes with 0.8 mL of a mixture of acetonitrile/water with 0.1% of formic acid. Under the optimal conditions, linearity was achieved for concentration levels ranging from 0.20 μg L−1 to 500 μg L−1, with regression coefficients (R2) in the range of 0.990 to 0.998. Limits of detection varying from 0.06 μg L−1 and 0.23 μg L−1 were attained, the relative standard deviations (n = 3) varied from 1.7 to 6.4, and the extraction recoveries ranged from 90.6% to 106.0% for all the analytes. The results of the presence of HAAs found in the river samples demonstrated levels ranging from 0.16 μg L−1 to 0.53 μg L−1; meanwhile, in the reservoir samples, the levels were higher, ranging from 0.37 μg L−1 to 0.93 μg L−1. Finally, a comparative discussion was applied to assess the greenness of approaches for the determination of heterocyclic aromatic amines in surface water using the available metrics.Laboratorio de Investigación y Desarrollo de Métodos Analíticos (LIDMA)