With the advantages of an engaged and authentic role-play game (RPG), this study aims to develop an RPG-enhanced English for specific purposes (ESP) vocabulary-acquisition framework, providing teachers and students a systematic way to incorporate RPG into ESP learning. The framework is composed of five parts: goal, three-level vocabulary sets, RPG contexts, a vocabulary test, and a participation questionnaire. In the perspective of three-level vocabulary sets, they are semantic sets, communicative sets, and situational sets. With regard to the vocabulary test, there are vocabulary assessment for semantic sets, vocabulary assessment for communicative sets, and vocabulary assessment for situational sets. In addition, the participation questionnaire classifies the students' participation scale into personal interest, external expectations, social contact, and social stimulation. To evaluate the framework effectiveness, eighty northern Taiwan vocational high school second-year students, divided into an experimental group and a control group, were recruited to participate in this study. The results confirmed that the framework can facilitate students' ESP vocabulary acquisition in vocabulary assessment for situational sets. Meanwhile, the framework was effective in promoting students' social participation, especially on external expectations and social contact perspectives.