This study aimed to find out how 21st-century skills can be integrated into ESP teaching using AI. As is known, 21st-century skills have an undeniable place in the globalized world. It is also a must for ESP students to survive in their academic and postgraduate lives. In that sense, AI can be a helpful way to integrate 21st-century skills into ESP teaching. For this aim, this systematic review explored new trends in English for specific purposes in the context of 21st-century skills by searching for related study areas and focusing on how artificial intelligence was integrated into ESP. Therefore, the literature was scrutinized using two key terms involving “ESP and 21st-century skills” and “ESP and 21st-century skills through AI” in Google Scholar. The dates were determined between 2015 and 2025 due to the aim and scope of this study. In total, there were 92 articles found; however, when these articles were investigated, 53 of them were eliminated because they were not related to the topic, which made the total number of articles 39. As a result, by shedding light on the current applications of 21st-century skills in ESP classrooms and their implementation via AI, this study underscored pedagogical implications involving how ESP teachers can embed 21st-century skills into ESP classes through AI, which can aid ESP teachers in meeting the needs of ESP students regarding the necessities of the rapidly increasing and demanding business and academic world.