The purpose of this paper aims to identify the components of service quality at specific tourist destinations and the crucial relationship between cultural contact and service quality in the Mekong Delta Region, Vietnam. The paper shows the relationship of tourists’ satisfaction, loyalty, and cultural contact after using the tourism service in the Mekong Delta Region, Vietnam based on qualitative and quantitative research. Data were obtained from 350 tourists, who responded willingly to a questionnaire-based survey. The results of the study show all factors were significant as components of service quality including tourism infrastructure, natural environment, human resources, safety and security, service, and price. All of these components and the cultural contact have an impact on tourist satisfaction and loyalty.