Appealing product characteristics, such as flavors, may stimulate e-cigarette use. While switching to e-cigarettes may reduce harm for smokers, concerns exist about e-cigarette use among never-smokers. The role of flavors in the decision to switch to or refrain from vaping is unclear. This study used a bottom-up approach to investigate the relation between flavor preferences and individual factors related to vaping between various user groups. A cross-sectional survey was conducted among never-users (n = 407), smokers (n = 138), dual users (n = 122), and exclusive vapers (n = 61) in the Netherlands. Demographics, attractiveness of product characteristics, flavor preferences, and individual factors related to vaping (knowledge, trust, perceived susceptibility, attitude, social influence, deliberation, and intention) were assessed. The availability of different flavors was the most attractive characteristic of e-cigarettes. Dual users and exclusive vapers had most often used tobacco and menthol/mint flavors when they first started vaping. Compared to dual users, exclusive vapers currently used more fruit and sweet flavors. Never-users who were interested in trying an e-liquid flavor had more knowledge about and a more positive attitude towards e-cigarettes. Smokers who were interested in trying a flavor had a more positive attitude towards e-cigarettes and experienced the social influence towards not using e-cigarettes as less strong than those who did not want to try any flavor. Hence, individual factors related to vaping differed depending on whether never-users and smokers wanted to try an e-liquid flavor. This means that flavors may moderate differences found in individual factors related to vaping, or vice versa.