Nanotechnology provides innovative and promising solutions for the conservation of cultural heritage, but the development and application of new nano-enabled products pose concerns regarding their human health and environmental risks. To address these issues, we propose a sustainability framework implementing the Safe by Design concept to support product developers in the early steps of product development, with the aim to provide safer nano-formulations for conservation, while retaining their functionality. In addition, this framework can support the assessment of sustainability of new products and their comparison to their conventional chemical counterparts if any. The goal is to promote the selection and use of safer and more sustainable nano-based products in different conservation contexts. The application of the proposed framework is illustrated through a hypothetical case which provides a realistic example of the methodological steps to be followed, tailored and iterated along the decision-making process.