High-tech agriculture is a leading trend, which is the key to the success of countries with developed agriculture and also the main path for sustainable agricultural development in the Mekong Delta. In recent years, the Mekong Delta has enhanced the application of technology in agricultural production, contributing to improving productivity and quality of agricultural products. However, high-tech agriculture is still relatively new in the Mekong Delta with many existing difficulties and inadequacies. This paper is to analyze the issues such as high-tech agriculture and its crucial role in the sustainable development of the Mekong Delta agriculture; current status, opportunities and challenges facing the Mekong Delta’s high-tech agriculture; directions, solutions and recommendations about policy mechanisms, the organizational model of the production, human resources, capital, science and technology and consumption market.