Nighttime vitality has garnered attention in recent years as an important indicator reflecting urban economy and quality of life. However, it is difficult to characterize this intangible issue. As a response, this study employed a data-driven approach to measure nighttime vitality and explored its relationships with urban spatial structure. Specifically, the data from Meituan.com—the largest Chinese shopping platform for local consumer products and retail services—were used to measure nighttime vitality based on a hierarchical weighting method. Multidimensional characteristics of the urban spatial structure were evaluated. Spatial regression models were conducted on the effect analysis of urban spatial structure on nighttime vitality. Relationship estimations were statistically significant with indicators, such as block functions, building density, interaction density, enclosure of locals, and the age structure of the main population. Our findings provide a more complete understanding of nighttime vitality, which is often overlooked in urban vitality studies. Insights derived from this study could help formulate spatial strategies to enhance nighttime vitality and quality of life.