Neonicotinoid insecticides (NNIs) are extensively utilized globally because of their efficient and broad-spectrum properties. However, their residues are also extensively distributed in the environment. Herein, MIL-101-SO 3 Na with abundant −NH− and sulfonate groups was synthesized via chloromethylation and nucleophilic substitution postmodification strategies and used to extract NNIs via solid-phase extraction. MIL-101-SO 3 Na was enhanced by introducing C−H•••N hydrogen bonds to strengthen interaction forces and −SO 3 Na groups to adjust surface charge and enhance electrostatic attraction. This modification and the substantial specific surface area (998 m 2 •g −1 ) of the metal−organic framework markedly enhanced the enrichment efficiency of MIL-101. The proposed method based on MIL-101-SO 3 Na exhibited a minimal detection threshold (0.04−0.87 ng•L −1 ), an extensive linear spectrum (1−2000 ng•L −1 ), and notable accuracy (a variation of 3.02−11.8%) in water and drink samples. NNI concentrations between 0.25 and 24.2 ng•L −1 in fruit juice and tea samples were accurately identified using the proposed method, demonstrating its feasibility in practical applications. The postmodification of MIL-101-SO 3 Na is an exceptional and promising approach for the sensitive detection of ultratrace NNI levels in complex matrices.