Understanding how genes and the environment interact to shape phenotypes is of fundamental importance for resolving important issues in adaptive evolution. Yet, for most model species with mature genetics and accessible genomic resources, we know little about the natural environmental factors that shape their evolution. By contrast, animal species with deeply understood ecologies and well characterized responses to environmental cues are rarely subjects of genomic investigations. Here, we preview advances in genomics in aphids and waterfleas that may help transform research on the regulatory mechanisms of phenotypic plasticity. This insect and crustacean duo has the capacity to produce extremely divergent phenotypes in response to environmental stimuli. Sexual fate and reproductive mode are condition-dependent in both groups, which are also capable of altering morphology, physiology and behavior in response to biotic and abiotic cues. Recently, the genome sequences for the pea aphid Acyrthosiphon pisum and the waterflea Daphnia pulex were described by their respective research communities. We propose that an integrative study of genome biology focused on the condition-dependent transcriptional basis of their shared plastic traits and specialized mode of reproduction will provide broad insight into adaptive plasticity and genome by environment interactions. We highlight recent advances in understanding the genome regulation of alternative phenotypes and environmental cue processing, and we propose future research avenues to discover gene networks and epigenetic mechanisms underlying phenotypic plasticity.