The internationalization of higher education has led to the increasing number of English as a Medium of Instruction (EMI) programs in contexts where English is not the first language nor the medium of communication, including Thailand. The introduction of EMI programs, however, is not without challenges. Therefore, a survey questionnaire was used to investigate the attitudes of engineering and nursing students toward EMI. Differences of attitudes based on the program of study, gender, nationality, year level, number of years studying English, the language of instruction in high school, Common European Framework of Reference for Languages (CEFR) level, and perceived proficiencies in speaking, reading, writing, and listening were explored. In addition, factors affecting the students’ EMI attitudes were known using exploratory factor analysis. Findings have shown significant differences in various aspects of EMI based on the program of study, CEFR level, and perceived proficiencies of the four macro language skills. Also, eight factors were elicited, including difficulties of the English language, availability of resources and opportunities, personal goals in life, limitations of time when studying content courses in English, providing activities to improve English language proficiency, enhancement of career goals, supports needed, and motivation and intercultural ability. Finally, implications were outlined to support the implementation of EMI, dubbed as an “unstoppable train”, in similar contexts like Thailand.