The modern agriculture system based on open-field crops requires a lot of energy and resources in terms of soil, water, and chemicals. Vertical farming (VF) systems could be a viable alternative for some types of cultivation that are receiving interest thanks to their high modularity, optimized water and nutrients use, and LEDs employment as an energy-efficient light source. However, VF design and installation are expensive and require well-tailored optimization depending on the specific crop to increase its competitiveness. This work analyzed the effects of different combinations of NPK (nitrogen-phosphorus-potassium) slow-release fertilizers and LED-based light recipes on the growth of baby leaf lettuce (Lactuca sativa L.), taking advantage of the Design of Experiments (DoE) methodology. The type of slow-release fertilizer, its quantity measured as the number of aggregates from 0 to 6, and the type of light recipe were considered as input factors, and their possible influence on the growth of lettuce (in terms of morphological parameters) in a controlled indoor farming system was measured. Results suggest that using higher fertilizer inputs equal to six aggregates leads to an increase of average leaf area equal to 46% (from 13.00 cm2 to 19.00 cm2), while the fresh weight of lettuce increases by 65% (from 1.79 g to 2.96 g). However, the height of plants also depends on the combination of the light recipes. In particular, the separate coupling of higher inputs of two fertilizers and light recipes leads to an increase in the height of lettuce equal to 33% (from 6.00 cm to 8.00 cm).