<p>The intensive and prolonged use of pyrethroids in mosquito control programs has led to widespread resistance in <i>Aedes aegypti</i>, thereby compromising the effectiveness of current interventions. Identifying insecticides with novel modes of action is therefore critical for resistance management and sustainable vector control. In this study, we examined three field populations of <i>Ae. aegypti</i> from northeastern Mexico previously characterized as pyrethroid-resistant. Resistance was confirmed using CDC bottle bioassays at discriminant concentrations of permethrin (15&#xa0;µg/bottle) and deltamethrin (10&#xa0;µg/bottle). Mechanisms of resistance were investigated through the detection of knockdown resistance (<i>kdr</i>) mutations (V410L, V1016I, F1534C) and measurement of detoxification enzyme activity, including esterases, cytochrome P450 monooxygenases (P450s), and glutathione S-transferases (GSTs). All populations exhibited resistance to pyrethroids, with significantly elevated P450 activity in all populations relative to the susceptible strain, whereas significant increases in α-esterase and GST activity were detected in only one population each. The most frequent multilocus <i>kdr</i> genotype was VL/II/CC, corresponding to a heterozygous genotype at locus 410 and homozygous mutant genotypes at loci 1016 and 1534. After confirming resistance, susceptibility was assessed against three non-conventional insecticides: indoxacarb, thiamethoxam, and chlorantraniliprole. Resistance ratios (RR₅₀ and RR₉₀) calculated relative to the susceptible New Orleans strain were &lt; 5 for all compounds and populations, indicating susceptibility. These results highlight the potential of non-conventional insecticides as alternative tools for managing pyrethroid-resistant <i>Ae. aegypti</i>. Their inclusion in resistance management programs through insecticide rotation and routine monitoring could enhance the sustainability of chemical control strategies.</p>