The research reported in this paper explores the impact of digital transformation as a disruptive innovation on manufacturing SMEs. The research is based on a qualitative Delphi study encompassing 49 experts from eleven EU countries. The paper aims to demonstrate how disruptive innovations affect organizational changes and determine critical factors in organizations that impact the initiating and promoting R&D of disruptive innovation. We discovered that disruptive innovations impact product/process development methods, new production concepts, new materials for products, and new organization plans. Additionally, we identified organizational changes related to the development and use of disruptive innovations in the future. We also indicate how disruptive innovations influence social and technological changes in the organizational environment. The analysis also disclosed three main groups of disruptive innovations and their impact on future smart factory development, namely the following: technological changes, the emergence of innovative products, business models and solutions and organizational culture as one of the crucial key success factors. The analysis also examined the enablers of the successful development/introduction of disruptive innovations, wherein internal and external factors were determined. Additionally, we presented obstacles and the approaches necessary to mitigate them. We can conclude from the findings that in the timeframe of 5-10 years, only the SME that uses/develops disruptive innovations will survive in the market. However, the companies do not always have a clear idea of the meaning of disruptive innovations. Therefore, it is important to set clear goals regarding the achievement of disruptive innovations in companies. It is also necessary to creatively apply presented instruments enabling improvement of organizational changes and apply some additional concepts, which we have suggested.