According to Knight, uncertainty signifies deviations from the expected states, which prevent us from the use of any probability for the determination of a result for a given action or decision [1]. This paper describes the phenomenon of uncertainty in the face of technological megatrends and challenges associated with them. The article focuses on the analysis of the uncertainty in one of the most important technology trends – the Internet of Things (IoT) – on the example of Healthcare. The right decisions are not always equivalent to good results. Sometimes, the decision taken in accordance with general rules brings worse results than the one who breaks them. Such a situation is possible as a result of the uncertainty accompanying the predictions of the future. In this article the concept of the IoT is treated as a big, complex, dynamic system with specific characteristics, dimensions. structures and behaviors. The aim of the article is to analyze the factors that may determine the uncertainty and ambiguity of such systems in the context of the development of Healthcare, and recommendations are made for future research directions.