The paper aims to examine the impact of different types of innovation on the performance of small and medium-sized enterprises (SMEs) in the Mekong Delta region. On the foundation of the resource-based view, the findings suggest that process innovation, organizational innovation, marketing innovation, and product innovation will create positive impacts on the performance of SMEs in the Mekong Delta region. Survey data were collected at89 SMEs in the Mekong Delta region, using the convenient random sampling method. Empirical results show that process innovation and product innovation help increase the performance of these enterprises. In addition, marketing innovation and organizational innovation are not statistically significant as these two types of innovation are still new concepts to SMEs in the Mekong Delta region, so it takes time to fully employ them. This study also suggests certain implications to help SMEs improve their efficiency in applying appropriate types of innovation.