This study examines the role of research and development (R&D) and nuclear energy in reducing fossil fuel-based energy losses in the United States (US) from 1990 to 2022. The analysis, based on annual data and advanced econometric techniques (Fourier ADL cointegration test, FMOLS, CCR, and DOLS), shows that renewable energy R&D effectiveness, energy efficiency investments, and nuclear energy contribute to reducing fossil fuel-based energy losses. Fossil fuel R&D investments increase energy losses, while renewable energy R&D effectiveness and energy efficiency investments reduce fossil fuel consumption. Nuclear energy continues to be a viable alternative to fossil fuels. However, it has been observed that fossil fuel R&D investments, along with increased efficiency, lead to greater resource use and higher energy losses. In this context, it is crucial to invest in environmentally friendly energy sources and improve the effectiveness of such investments to reduce inefficiencies in fossil fuel use. Future studies could provide deeper insights into reducing dependency on fossil fuels by examining the long-term effects of renewable energy policies.