Spodoptera frugiperda (J.E. Smith) (Noctuidae: Lepidoptera) is a notable insect pest that invades major cereal crops, causing significant damage and loss. Resistances of 2nd instar larvae of two Egyptian field populations of S. frugiperda, collected from the Fayoum and Giza governments, were measured against eight insecticides, including traditional insecticides (profenofos and cyperme-thrin), bio-insecticides (emamectin benzoate, spinosad, and Bacillus thuringiensis), and insect growth regulators (IGRs) (lufenuron, diflubenzuron, and methoxyfenozide). In addition, the synergistic effects of three synergists (Piperonyl butoxide (PBO), diethyl maleate (DEM), and triphenyl phosphate (TPP) were assessed, and the activities of detoxification enzymes (acetylcholine esterase (AChE), cytochrome P-450 (CYP-450), carboxylesterase (CarE), and glutathione-s-transferase (GST) were also determined. Resistance surveillance revealed that the Fayoum field population showed moderate resistance to cypermethrin (RR = 5.75-fold), followed by spinosad (RR = 2.62-fold), and lufenuron (2.01-fold). On the other hand, the Giza population exhibited significant resistance to cypermethrin only (RR = 3.65-fold). Our results revealed that emamectin benzoate was the most effective insecticide , with an LC 50 value of 0.003 mg/L for the Fayoum population and 0.001 mg/L for the Giza population, compared to the susceptible strain (0.005 mg/L). Among the biological insecticides, Bacillus thuringiensis was the least toxic insecticide of all the tested strains. Synergism assays indicated that DEM and TPP had the most synergistic effect on spinosad (SR = 8.00-fold for both), followed by PBO (SR = 5.71-fold) for the Fayoum population, compared with spinosad alone. The assay of detoxification enzymes showed that GST activity significantly (p < 0.05) increased in the two field strains compared to the susceptible strain. However, no significant changes were observed among the tested strains in CYP-450, CarE, or AChE. The findings of this study provide substantial insights into tracking and managing the development of insecticide resistance in S. frugiperda in Egypt.