Science dynamics has become an established part of scientific research. Over the past years, a broad variety of experimental approaches has been developed to explore the frontiers of the current state of the art -and their shifts- in either separate disciplines or scientific domains, such as expert-opinion consultations, multi-level approaches, living labs, joint decision rooms, scenario methods, imagineering experiments, or interactive envisioning methods. The present chapter will contribute to science dynamics in regional science research by offering findings from an envisioning experiment among some 60 well-known regional scientists, with a view to a critical assessment of past and current performance, so as to initiate an open exploration of promising and challenging research endeavours for the next decades of regional science research. This may range from innovative concept formulation to joint use of open access and big data. This experimental approach serves to pave the road towards proactive strategies and conceptualisations in regional science research and regional policy. The main future concern implicit in the brainstorming experiment appears to be related to spatial justice, next to good governance, and consistency between techniques, methods and theories, as well as an effective interaction with students/scholars and society. This exercise shows that important lessons can also be learned from past scientific mistakes, especially those that were associated with policy failures. New scientific ideas are, of course, pushed by the rise of novel techniques and methods, but also and predominately from evolving new realities, either social or technological. Nevertheless, there are still various doubts concerning the future direction of regional science agenda: Which new thoughts and methods are requested? Which policies must be created and improved? What are the scientific possibilities created by new data? The regional science agenda is full of challenges and promises, but how can it be effective? This scoping study does not provide definite answers, but serves to explore uncertain future frontiers.