Papua New Guinea’s economic structure has been reliant on the extraction of natural resources such as minerals, crude oil, and gas. While the extractive industry has driven national growth and ensured economic stability since independence, it has limited diversification and innovation. There are studies on higher education, research and human capital development. However, there is limited and disparate literature on science policy and knowledge-based economy models and its application to the PNG context. This paper examines the challenges and enablers for PNG to transition toward a knowledgebased economy. The study identifies significant policy, infrastructural, and socio-cultural challenges. Conversely, realigning research institutions, investment in research infrastructure, and collaboration are key enablers. The paper concludes that investment in research, science and innovation is crucial for a knowledge-driven economy.