Abstract Background In the shifting paradigm of tobacco use, the attitudes of non-smokers toward e-cigarettes are crucial for public health planning, as in the literature it has been suggested that non-smokers who use e-cigarettes could be more prone to switch to tobacco. This multi-center study investigates the interplay between traditional smoking and the potential benefits of transitioning to e-smoking, through a comprehensive examination of smoking behaviors, dietary, and lifestyle practices. Methods MINERVA (My changINg lifEstyles, our Research, and eVeryone’s heAlth) is an ongoing prospective international cohort study aimed at investigating the association between smoking habits and dietary and lifestyle habits among the study participants. The secondary objective pertains to the assessment of subjects’ willingness to try e-cigarettes. We implemented an univariable logistic regression analysis on a dataset comprising 2367 nonsmokers to identify factors influencing their willingness to smoke e-cigarettes. Results Employment significantly predicted willingness, with employed non-smokers showing a higher likelihood to consider e-smoking (OR 2.5, p = 0.002). Household dynamics, specifically the presence of children, also affected the decision, indicating a protective effect against adopting e-smoking (OR 1.26, p < 0.001). Lifestyle choices, particularly fitness and dietary habits, played a discernible role. Surprisingly, age inversely correlated with the willingness to try e-smoking, as younger non-smokers were more likely to consider it (OR 0.97 per year increase, p < 0.001), suggesting that this openness could increase their risk of future tobacco use, which carries important public health consequences. Conclusions The study’s outcomes underscore the impact of socio-economic and lifestyle factors on non-smokers’ openness to e-cigarettes. These insights are pivotal for devising culturally competent educational campaigns and regulatory policies. Key messages • In the shifting paradigm of tobacco use, the attitudes of non-smokers toward e-cigarettes are crucial for public health planning. • By thoroughly analyzing smoking habits, diet, and lifestyle choices, the Minerva Project research aims to shed light on the complex dynamics between health behaviors and smoking.