Repurposing plant crops as biofactories was constrained in the past by the requirement for transgenic modification at various points in the development process, and the accompanying regulatory burden, particularly in Europe. However, very recently, a group of New Plant Breeding Techniques (NPBTs) have emerged bringing unprecedented opportunities for Plant Biotechnology. Breeding a tobacco-based biofactory crop for high value non-smoking products is now possible with the use of NPBTs. Four of those NPBTs, namely sequence-specific nuclease (SSN)-mediated genome editing, cis/intra-genesis, grafting and agroinfiltration, are especially useful in Molecular Farming, as they serve to breed efficient biofactories while circumventing the need for transgenic modification in the cultivation phase.