Smartphones have become an intimate friend and very close to the young people. The explosion in smartphone technologies and the great utilities that smartphones provide by rich and flexible applications are a solid foundation for the development of smartphone advertising. For this reason, the online advertising targeted at youth through smartphone is expected to boom in the near future. This study attempts to develop a comprehensive research framework to investigate the factors impacting on the attitudes and response of Vietnamese young people aged 18-32 to smartphone in-app advertisements. The empirical result illustrated that the credibility, informativeness and entertainment are the main factors influencing on the attitudes of young customers. Additionally, the user experience significantly moderates the relationship between acceptance of smartphone technologies, attitudes and response to smartphone in-app ads. The moderating effect of permission and personalization is explored as the factors determined the perceived irritation by smartphone in-app ads less effective.