The potato (Solanum tuberosum) is a staple food worldwide, but modern potato cultivation relies heavily on the use of pesticides to control pests and diseases. However, many wild Solanum species are highly resistant to biotic and abiotic stresses relevant to potato production. Several of these species have been used in potato breeding to confer resistance, which has only been moderately successful due to linkage drag and sexual incompatability. Instead, we propose an alternative approach to utilizing the potential of wild Solanum germplasms. Recently, de novo domestication has been suggested for creating more resilient crops: instead of introducing resistance genes into existing crops, domestication traits could be introduced into resistant wild crop relatives to create new crops. To select the right candidate for de novo domestication, we evaluated the 107 known wild tuber-bearing Solanum species for their resistance to biotic and abiotic stresses based on the existing scientific literature and characterized selected species experimentally. Based on this, the highly pest- and disease-resistant species, S. bulbocastanaum, was chosen. Our results showed that it produced relatively large tubers, even under long-day conditions, and performed exceptionally well in tissue culture. Successful genetic transformation is essential for introducing domestication traits and often constitutes the biggest hurdle to de novo domestication. We were able to produce genome-edited S. bulbocastanum plants via protoplast transformation. This opens the door for targeting domestication traits such as long-day tuberization, a low glycoalkaloid content in tubers, short stolons, etc.