Grapes, as the most important and economically significant horticultural product in the Sistan region, play a pivotal role in the region's economic structure. Given the dominance of grape cultivation and its considerable impacts on the economic, social, and environmental aspects of the region—key components of sustainability—assessing sustainability levels and identifying factors threatening it is an effective step towards strengthening the production model of this crop. The main approach of this study is a survey, and in order to evaluate the sustainability of grape orchards in the region and identify the factors affecting it, data from the 2019–2020 crop year was utilized. These data were collected through 86 questionnaires, randomly distributed among the region’s farmers. In the first stage, after identifying and developing sustainability measurement indicators, the indicators were scaled using the method of scale discrepancy resolution and then weighted through Principal Component Analysis (PCA). The findings show that more than half of the grape orchards in the region are in a relatively unsustainable condition. Moreover, the results of stepwise regression analysis indicate that factors such as production, orchard area, number of trees, labor, animal manure usage, farming experience, and education level are among the most significant factors influencing the sustainability index. In contrast, inputs such as chemical fertilizers and pesticides had minimal impact, and receiving loans had a negative effect on sustainability.