By using the combination of several regression techniques on panel data, this study explores the influence of human capital, institutional quality, and the Fourth Industrial Revolution on unemployment rates in 46 Asian countries during the period from 2007 to 2020. According to the generalized method of moments (GMM), there are a total of 9 factors affecting the unemployment rate in the researched model, including high-tech exports, inflation, population, gross domestic product, government spending, foreign debt, foreign direct investment, human capital, and institutions. This result confirmed that high-tech development increases unemployment in Asia; however, the nexus between human capital and institutional situation with the unemployment rate is different based on the particular fields. Moreover, some policy implications also have been suggested to reduce unemployment in Asian countries in the context of the Fourth Industrial Revolution.