Sustainability is the most critical point in micro-scale indoor crop systems. It can be improved through the optimization of all of the production factors, such as water, nutrients, and energy. The use of light-emitting diodes (LED) allows the fine regulation of the light intensity and light spectrum to be obtained, with a significant reduction in energy consumption. The objective of this study was the optimization of a LED-based protocol of light management for Romaine lettuce cultivation in a micro-growing environment specifically designed for home cultivation. Four different growing cycles were tested. In each one, the light spectrum was modified by increasing the percentage of red light and decreasing the blue light. This resulted in a change in the light intensity which ranged from 63.2 to 194.54 µmol m −2 s −1 . Moreover, the photoperiod was shortened to reduce the energy consumption and, in the last cycle, the effect of the daily alternation of dark and light was tested. The fresh and dry biomass produced were measured and the energy consumed in each cycle was monitored. The quality of lettuce was evaluated by measuring several physiological indexes, including chlorophyll a fluorescence, chlorophyll, sugars, nitrate, lipid peroxidation, carotenoids, and phenolic index. The results obtained showed that the productivity and the quality of lettuce can be positively affected by modulating the light quality and intensity, as well as other cultural practices. At the same time, the estimation of the electrical energy consumption indicated that little changes in the lighting recipe can significantly affect the energetic, environmental, and economic impact of home productions.