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Fertilization with variable rate technology (VRT) is a pivotal technique of precision agriculture proposed for eco-friendly farming practices. Yet the magnitude of environmental benefits is often not well known or is highly variable. This study used a multi-indicator model and life cycle-based indicators to compare the performance of rain-fed durum wheat production using uniform (UA) and variable N fertilization (VRT). Two functional units were used: 1 ha of cultivated wheat and 1 ton of wheat produced. The energy analysis indicated that VRT increases energy use efficiency and productivity by 13.3%, reduces specific energy and total energy input by 11.7%, and increases net energy gain by 15.3%. The life cycle assessment (LCA) analysis indicated that for some environmental impacts, VRT had minor negative effects due to the comparable yield performance with UA. Yet, the VRT had a noteworthy positive impact on global warming, fine particulate matter formation, stratospheric ozone depletion, terrestrial acidification, and marine eutrophication, generating a final environmental benefit of 12.2% for 1 ton of product and 13.3% for 1 ha of land. Economic valuation or monetization of LCA results using monetization weighting factors indicated indirect economic benefits of VRT can be up to 6.6% for 1 ton of product and 7.7% for 1 ha of land. Our findings support the use of nitrogen fertilization with VRT for sustainable extensification and improved eco-efficiency of wheat production in a Mediterranean context. As a result of our research, we conclude that future case studies on annual crops with moderate land requirements should employ multiple metrics and functional units, as well as the concepts of monetization and life cycle assessment, to investigate trade-offs between yield, economic, and environmental benefits and to aid decision-making about the true sustainability of proposed farming technologies. [ABSTRACT FROM AUTHOR]