The development of Quality Protein Maize (QPM) with high levels of lysine and tryptophan in grain has opened ways of using maize to supply the two essential amino acids. Being developed by combining the genetic system of opaque-2 gene and o2 endosperm modifiers, it was not well understood how nitrogen and water deficiencies could affect its characteristics. This study was undertaken to know the influence of N and water stresses on gene action and the effects of genotypes × environments interaction in QPM. It was found that N and water deficiencies influenced the gene action and suppressed the action of o2 endosperm modifiers making QPM to revert partially or totally to o2 maize state. This may have negative consequences on cultivation of QPM in nitrogen and water stress prone regions.