A group of New Plant Breeding Techniques (NPBT) has opened unprecedented opportunities in agriculture. Those NPBTs are at least as efficient and often more precise than previous traditional and GM techniques, while circumventing the introduction of heritable transgenes from distant species in the plant genome. Properly communicated, NPBTs are expected to gain wide acceptance, especially when applied to breeding objectives which are seen as beneficial for the society. A well-perceived objective is Molecular Farming, which refers to the use of plants for the production of valuable biomolecules (e. g. biopharmaceuticals). Cultivated tobacco (Nicotiana tabacum) and its close Australian relative Nicotiana benthamiana, are preferred species in Molecular Farming due to their favourable features: non-food crops, easy tissue regeneration, high productivity, rich secondary metabolism and availability of genetic tools. In sharp contrast, traditional tobacco cultivation is in serious decline in the EU, causing serious social problems in many rural areas. NEWCOTIANA aims to revitalize those areas by breeding efficient Nicotiana biofactories of high-value non-smoking products as alternatives for traditional tobacco crops. NEWCOTIANA will develop the most advanced tobacco NPBTs toolbox, easily transferable to other plants. This will position EU in the avant-garde of breeding innovation. This toolbox will be used to create elite multipurpose Nicotiana varieties improved in product-specific traits (bioproduct quality, stability and yield), next to more general traits as biomass, resilience and biosafety. The “Newcotiana” varieties will be carefully tested in relevant pre-industrial environments for the production of end-value chemicals, namely proteins and metabolites for health and nutriceutical use. Ethical, social and legal aspects will be closely monitored and public and stakeholder engagement will be assured using innovative science communication methodologies.