Along with the number of Facebook users in Vietnam are increasing, online shopping takes advantage their features available which has also been rapidly developed and expanded. This paper focuses on the shopping behavior and determinants affecting the decision of online shopping from Facebook Users in the Mekong Delta. The data used for this research was collected by making surveys of 350 observations in 13 provinces living in the Mekong Delta River of Vietnam by structured questionnaires. These two analysis methods namely Exploratory Factor Analysis and logistic regression model are used to analyze the factors that affecting online shopping decisions among Facebook Users. The findings revealed that these factors have a positive influence on online purchasing decision of such users include the belief in online shopping, the convenience and comfort of online shopping, the variety of products and the influence of Facebook surfing habit. In addition, factors of product (fake) risk and financial risk showed negative impacts on online shopping Facebook Users. Besides, the demographic characteristics such as age, gender and the amount of time consumers spend on Facebook also illustrated effect to such shopping behavior. Finally, some management implications to enhance the attractiveness and competitiveness of online shopping for users in the era of technological development (4.0) will be conducted and provided from this research.