During the last two decades, the concept of eco-efficiency has been recognized as a suitable measure of progress towards a greener and more sustainable economy. The prefix “eco-” refers to both economic and ecological (environmental) performance. The need for improving eco-efficiency leads to the challenge of identifying the most promising alternative solutions which improve both the economic and the environmental performance of a given system (“eco-innovations”). Therefore, it becomes critical to develop eco-efficiency metrics for measuring environmental and economic performance of a system. The current paper presents a methodological framework that attempts to explore the use of eco-efficiency indicators in meso-level water use systems and through them to assess the impact of innovative technologies in such systems. The assessment of the environmental performance follows a life cycle-oriented approach using the midpoint impact categories while the economic performance is measured using the total value added to the product due to water use. The eco-efficiency is expressed as the ratio of the economic performance indicator to the environmental performance indicator. The proposed approach is applied to a water use system of the agricultural sector, and more specifically to the fresh form tomato crop production in Phthiotida. The analysis reveals that the most important environmental impacts of the system are (a) greenhouse gas emissions due to energy consumption, (b) release of toxic substances, due to the use of fertilizers and pesticides, and (c) depletion of freshwater resources. Three alternative interventions are examined for upgrading the value chain: (a) installation of subsurface drip irrigation (SDI) system, (b) replacement of diesel pumps with solar pumps, and (c) use of organic fertilizers. Based on the findings, all of the proposed interventions have a positive impact on the overall eco-efficiency of the system. SDI is the least favorable mainly due to its high investment cost. The use of solar pumps strongly influences climate change and photochemical ozone formation while the use of organic fertilizers has a more balanced impact on all indicators, with an emphasis on eutrophication. Thus, for a more holistic approach, regarding the eco-efficiency performance, a combined application of these three scenarios may be proposed.