Economic potential plays the pivotal role in the regional development and the high level of it leads to regional sustainability. Demographic change, economic performance, labour force potential, innovation capacity, investment inflows are the key elements of regional potential assessment. Conducting assessment of regional economic potential is a part of Smart specialisation framework, which identifies the priorities of regional innovation policy. Existing methodologies are not always applicable in the terms of emerging economies. Therefore, the alternative assessment method of regional economic potential is offered in the article, which includes a set of regional development indicators. The purpose of the article is to conduct an assessment of regional economic potential using simulating equations and to define the impact of relevant indicators on its formation. In the article the authors developed the model of economic potential assessment based on systems of simultaneous equations and its step-by-step algorithm of realization. This mathematical apparatus allows to identify the links between the key (basic) factors that are the formative (determining) complex economic objects, which is the economic potential of the region. The use of systems of simultaneous equations is relevant for different areas of study: forecast, management or scenario calculations, which could be widely used in Smart specialisation processes. The research results will be useful for key stakeholders of Smart specialisation project (regional authorities, business, academic sector and NGOs) in order to choose the priorities of regional innovation policy during Entrepreneurial discovery process. The research is done within the project “The SMEs’ development models in the context of regional Smart Specialisation”.