Changing climate is putting a severe strain on crop production. New breeding methods are urgently needed to cope with abiotic stresses such as drought, high temperature, and soil salinity. Crop wild relatives (CWRs) have long been used as sources of genetic variation to improve stress resistance. However, the multigenic nature of resistance traits makes it very difficult to use conventional breeding (i.e., wide crosses followed by selection). The advent of gene editing (GE) techniques now makes it possible to manipulate CWRs to improve their agronomic value, through a platform known as de novo domestication. The Solanaceae family has been intensely studied due to their profusion of valuable CWRs with cultivation potential. Here, we summarize and discuss the prospects for de novo domestication in CWRs via GE for two major solanaceous crops: tomato (Solanum lycopersicum) and potato (S. tuberosum).