The increasing application of process-oriented approaches in new challenging dynamic domains beyond business computing (e.g., healthcare, emergency management, factories of the future, home automation, etc.) has led to reconsider the level of flexibility and support required to manage complex knowledge-intensive processes in such domains. A knowledge-intensive process is influenced by user decision making and coupled with contextual data and knowledge production, and involves performing complex tasks in the “physical” real world to achieve a common goal. The physical world, however, is not entirely predictable, and knowledge-intensive processes must be robust to unexpected conditions and adaptable to unanticipated exceptions, recognizing that in real-world environments it is not adequate to assume that all possible recovery activities can be predefined for dealing with the exceptions that can ensue. To tackle this issue, in this paper we present SmartPM, a model and a prototype Process Management System featuring a set of techniques providing support for automated adaptation of knowledge-intensive processes at runtime. Such techniques are able to automatically adapt process instances when unanticipated exceptions occur, without explicitly defining policies to recover from exceptions and without the intervention of domain experts at runtime, aiming at reducing error-prone and costly manual ad-hoc changes, and thus at relieving users from complex adaptations tasks. To accomplish this, we make use of well-established techniques and frameworks from Artificial Intelligence, such as situation calculus, IndiGolog and classical planning. The approach, which is backed by a formal model, has been implemented and validated with a case study based on real knowledge-intensive processes coming from an emergency management domain.