Vacation decision-making is critical in the global tourism industry as it influences travelers’ destinations choice, duration, and spending. Understanding the underlying factors that influence vacation decision-making is critical for both tourists and destination marketers, as it can help to customize marketing strategies to improve the overall quality of tourism offerings. The present study aimed to explore the effect of destination image, tourist perceptions of safety, availability of regenerative tourism activities, and hotel’s green reputation on vacation decision-making, as well as the mediating role of perceived quality of destination and the moderating role of previous traveling experience. Data was collected from a sample of 350 tourists who have recently visited an eco-friendly destination and analyzed using SmartPLS v.4.0. The results showed that destination image, tourist perceptions of safety, availability of regenerative tourism activities, and hotel’s green reputation have a significant effect on vacation decision-making, with a significant mediating effect of perceived quality of destination and moderating effect of previous traveling experience. These findings provide valuable insights into the factors that influence vacation decision-making, especially the emerging role of regenerative tourism activities, and hotel’s green reputation in the global tourism industry.