In order to succeed in a competitive environment, enterprises and organizations must quickly respond to external influences, such as digitalization, expansion of information exchange, and challenges caused by Industry 4.0. High-tech knowledge-intensive enterprises that develop and commercialize their original innovative products and technologies as well as provide intellectual services in the field of high technologies are the first to respond to such challenges. A number of works on how the digitalization in economy impacts organizational and managerial activities of enterprises, their R&D, and creation, production and commercialization of innovative products are analyzed. As the results of the study, a number of properties and patterns that determine the successful adaptation of innovative enterprises to the challenges of Industry 4.0 wereidentified. Among them there are material resources, including technology and equipment, scientific and technological achievements, financial, personnel and information support and adaptive organizational and economic capabilities. It is shown that in order to adapt to the challenges of Industry 4.0, enterprises must match capabilities of the digital economy with their material, intellectual and production resources using innovative potential as a measurement tool. It is determined that the procedures for assessing the innovative potential of enterprises can become an effective tool for assessing both quantitative/qualitative indicators of enterprises and degree of their adaptation to the challenges of Industry 4.0. The proposed methodology for a comprehensive assessment of industrial enterprises’ innovative potential as the degree of their adaptation to the challenges of Industry 4.0 was implemented at the high-tech knowledge-intensive enterprises “Shtorm” and “Tekhnotron”. Both of them are well known for their innovative developments in the field of welding production. It was demonstrated that the proposed methodology allows not just assessing the degree of adaptation to the digital economy and the challenges of Industry 4.0, but also assessing the impact of planned activities on innovations and determine methods and means of responding to the changes in external and internal environment of enterprises.