The present study addressed skills mismatch in the context of large-scale manufacturing industries adopting Industry 4.0 technologies in Türkiye. In this qualitative study, we held face-to-face interviews with 41 participants consisting of senior managers, human resources directors, and experts implementing the Industry 4.0 process of 19 large-scale manufacturing companies operating in seven provinces of Türkiye (Istanbul, Ankara, Izmir, Izmit, Kayseri, Bursa, and Gaziantep). The findings demonstrated four main categories where we discussed the reasons for skills mismatch in the companies in the transition to Industry 4.0: difficulties in labor supply, difficulties in retaining the labor force, labor force’s Adaptation to Industry 4.0, and the emergence of novel business models.