Urban agriculture is found to be one of the ways to produce process and sell food and other products within and around cities and towns. Urban agriculture takes varied forms including backyard gardens, community gardens, small-scale commercial growing, hydroponic, aquaculture and livestock rearing. Hydroponics is gaining global attention in crop cultivation. The objective of the present study was to assess optimization of nutrient supply and locally available growing media selection for small-scale hydroponic production of lettuce (Lactuca sativa L.) in Bahir Dar, Ethiopia. The experiment was done in a factorial design. The factors of the experiment were daily nutrient supply frequency with three levels (Once, Twice and Three times per day) and growing media (Sawdust, Rice husk and Mixture of the two media). According to the overall factorial analysis growing media had a significant effect (P < 0.05), on lettuce biomass, leaf moisture content, leaf area, and root shoot ratio, leaf dry weight and leaf fresh weight (marginally significant). In addition nutrient supply frequency had a significant effect (P < 0.05) on lettuce biomass, leaf moisture content, and number of leaves, leaf area, leaf dry weight and leaf fresh weight. Growing media and nutrient supply interaction had a significant effect on biomass, moisture content, leaf area and leaf dry weight at P-value < 0.05, 95% confidence interval. Treatment supplied with nutrient once a day and rice husk produced the highest biomass and leaf dry weight. However, root shoot ratio was the highest in nutrient supplied twice a day compared with the rest of experimental combinations. Moisture content and leaf number grown in sawdust is statistically significant when nutrients supplied twice a day compared to the rest media used. Excess application of nutrient supply minimizes the growth and yields of lettuce. Therefore, the optimum amount of nutrient that should be supplied for a small scale hydroponic is once a day. More information about hydroponic techniques and performing experimental studies to show the benefits of hydroponic technology is vital. Key Words: Factorial design, Hydroponic, Growing media, Lettuce, Urban agriculture.