Cyst nematodes consistently threaten agricultural production, causing billions of dollars in losses globally. The (Resistance to 1) locus of soybean () is the most popular resistance source used against soybean cyst nematodes (). is a complex locus that has multiple repeats of a ~30 kilobase segment carrying three genes that contribute to resistance. We investigated if soybean could function in different plant families, conferring resistance to their respective cyst nematode parasites. Transgenic and potato () plants expressing the three soybean genes were generated. The recipient Brassicaceae and Solanaceae plant species exhibited elevated resistance, respectively, to and to and . However, some negative consequences including reduced root growth and tuber biomass were observed upon expression in heterologous species. One of the genes at encodes a toxic version of an alpha-SNAP protein that has been demonstrated to interfere with vesicle trafficking. Using a transient expression assay in , native and potato alpha-SNAPs (Soluble NSF [N-ethylamine sensitive factor] attachment protein) were found to compensate for the toxicity of soybean alpha-SNAP proteins. Hence future manipulation of the balance between alpha-SNAP and the endogenous wild-type alpha-SNAPs (as well as the recently discovered soybean NSF-RAN07) may mitigate impacts of on plant productivity. The multi-species efficacy of soybean demonstrates that the encoded mechanisms can function across plant and cyst nematode species, and offers a possible avenue for engineered resistance in diverse crop species.