In response to the pressing need to motivationally empower people to persevere in travel pursuit despite challenges, this study proposes the facilitation of self-determined travel motivations as a promising approach. Additionally, the possible mechanism and effectiveness variation of such facilitation across different challenge levels is also proposed and examined through a quasi-experimental design, and analyzed with a new test of moderated mediation based on Hayes’ (2015a) model. By examining people with mobility impairments (PwMI), the results indicate that given significant travel challenges, the travel facilitation should prioritize the cultivation of intrinsic travel motivation over less-autonomous motivations; and foster perceived travel competence more than autonomy or relatedness. Such cross-context exploration extends the Self-determination Theory with a new moderator, challenge levels. The adopted new moderated-mediation analysis has competitive accuracy, efficiency, and robustness for less-controlled real-world tourism experiments. The individual/context-based motivational programs can be derived to maximally encourage travel pursuits despite challenges.