We explored the possibility of Plutella xylostella (L.) developing resistance to indoxacarb with one mode of action and a grower standard, Neemazal-F^TM, as a proxy for one insecticide, Azadirachtin with multiple modes of action and crude aqueous Neem Seed Kernel Extract (NSKE) having multiple chemicals and multiple modes of action. A selection pressure of 72 to 82 % was applied over generations. Indoxacarb selected JInd-R strain recorded 249-fold resistance in 14 generations while Neemazal-F^TM and NSKE selected strains recorded just around 2-2.25 fold resistance. Slopes of LC₅₀ values over generations were observed to follow significantly different trajectories (ANCOVA: F_2,19=21.364; p<0.05) with JInd-R recording the highest slope (b=0.3379). Heritability (h²) and response to selection (R) were highest for JInd-R (h²=0.307; R=0.16) and very low for JNSKE-R (h²=0.013; R=0.010) strains. It was estimated that at 90 percent selection pressure JInd-R strain required 4-5 generations while JNSKE-R needed >70 generations for a 10-fold increase in resistance (G). Poor response of P. xylostella for selection against Neemzal-F^TM and NSKE may be due to multiple components of neem affecting insect behavior, physiology and biology in various ways, resulting in ‘physiological inability in the insect to recognize the stress (PIRS)’ leading to built-in resistance prevention mechanism against insects. Therefore, neem remains a potentially valuable and sustainable insecticide for long term use in insect pest management.