The trend to Industry 5.0 is a severe change from the completely automated and machine-driven patterns of the previous industrial revolutions. Although the technological potential of automation, artificial intelligence (AI), robotics, and the Internet of Things (IoT) is steadily increasing, the mass implementation of these developments is highly obstructed. The barriers, which range from technological constraints to regulatory uncertainties, are a challenge to organizations that wish to incorporate advanced systems in their current operations. These challenges should be overcome to take full advantage of Industry 5.0. In this chapter, the author penetrates into the main challenges that prevent the shift to Industry 5.0, including integration complexity, financial constraints, cultural resistance, and policy gaps. Through these questions and answers to these questions, we hope to give a clear guideline to the industries that wish to succeed in this new age of human–machine interaction.