Nowadays, innovation has become an extremely important policy imperative for all countries involved in building a knowledge-based society. As a catalyst for economic growth, research and innovation, it is identified as a generator of solutions to overcome any challenge. Increasing the role of innovation in enhancing economic competitiveness, as well as the need to strengthen cooperation between academia and business environment are desiderata contained in a number of policy documents. Analysis of the legislative and policy framework, situation in the field of research and innovation and economic development in the Republic of Moldova reveals certain deficiencies, including the fragmentation of the system and the national policy for research and innovation to the detriment of a systemic and integrated approach; insufficient interaction of innovation policy with other national, regional, local and sectoral policies; priorities and goals of strategies are not convergent, they are mostly limited by their own areas of action; development policy is insufficiently focused on capitalizing on the competitive potential based on innovation, on the synergy of resources that can ensure economic growth; regional development focuses mainly on infrastructure development; the allocation of resources for research, development and innovation is fragmented and based more on institutional research capacity than on the needs of the real sector of economy, which generates gaps in cost and benefits, etc. In such a context, there is an urgent need to change the paradigm of economic development, rethink the system of research, development and innovation (RDI) and regional development and identify opportunities for economic transformation based on innovation. An effective solution in this regard is economic growth and competitiveness through smart specialization, which is considered an innovative strategy for economic transformation at local/regional/national levels. While in the EU countries the development and implementation of smart specialization strategies have become a prerequisite for demonstrating positive results, in the Republic of Moldova this process is in its infancy and requires enhanced efforts from all stakeholders in accomplishing this approach. The paper analyses trends in research, development and innovation in the Republic of Moldova, the challenges it faces, the actions taken in the context of developing the smart specialization strategy and identifies future goals for innovation-driven economic transformation. The development and implementation of the Smart Specialization Strategy in our country will play an essential role in regional development, increasing competitive economic advantages, by identifying new niches of innovative specialization or by integrating new technologies into traditional industries and exploiting their „smart” potential. This will facilitate the transformation of the republic’s economy into a knowledge-based economy, competitive, sustainable and integrated into international value chains.