Aquaculture is vital for feeding a growing population as aquatic creatures require more protein. Utilizing protein-rich biomass for feeding animals is a possible solution. Biorefinery technology can extract protein and non-protein components from biomass, creating an economically feasible value chain. This study replaced fish feed with napier grass and used a compensatory response to reduce the cost of feeding Nile tilapia. The trial involved dividing mono-sex male Nile tilapia, initially weighing between 11.10 and 13.60 g/f, into four groups with three replications based on their feeding regime. Therefore, in the study, four groups of Nile tilapia were fed different diets for 90 days. The control group (T1) received a commercial floating pellet diet throughout the trial. Group T2 and T3 received a mix of commercial floating pellet diet and napier grass in varying proportions, and group T4 was fed with only napier grass throughout the trial. The study found that groups T2 and T3 had remarkable fish growth performance, high digestibility of napier grass, and lower feed prices with the highest benefit-cost ratios. The percentage of edible flesh and Hepatosomatic Index (PT2) were higher in group T2 than T3. Cellulase activity decreased with the frequency of napier grass intake, and the amylase activity was higher in T2 than T3, which also had the highest growth performance and feed utilization. Therefore, the study suggests that the optimal feeding regimen for Nile tilapia is T2 or T3, which promotes growth and is cost-effective.