Efficient postmining reclamation requires successful revegetation. By using RNA sequencing, we evaluated the growth response of two invasive plants, goutweed (Aegopodium podagraria L.) and mugwort (Artemisia vulgaris), grown in two Appalachian acid-mine soils (MS-I and -II, pH ∼ 4.6). Although deficient in macronutrients, both soils contained high levels of plant-available Al, Fe and Mn. Both plant types showed toxicity tolerance, but metal accumulation differed by plant and site. With MS-I, Al accumulation was greater for mugwort than goutweed (385 ± 47 vs 2151 ± 251 μg g-1). Al concentration was similar between mine sites, but its accumulation in mugwort was greater with MS-I than MS-II, with no difference in accumulation by site for goutweed. An in situ approach revealed deregulation of multiple factors such as transporters, transcription factors, and metal chelators for metal uptake or exclusion. The two plant systems showed common gene expression patterns for different pathways. Both plant systems appeared to have few common heavy-metal pathway regulators addressing mineral toxicity/deficiency in both mine sites, which implies adaptability of invasive plants for efficient growth at mine sites with toxic waste. Functional genomics can be used to screen for plant adaptability, especially for reclamation and phytoremediation of contaminated soils and waters.