Technical Abstract: Twenty seven isocaloric (3.05 kcal/g) ingredient blends were factorially formulated using three levels each of DDGS (20, 25, and 30% db), protein (30, 32.5, and 35% db), and feed moisture content (25, 35, and 45% db), along with appropriate quantities of cassava starch, soybean meal, fish meal, whey, vitamin, and mineral mix to produce a balanced diet for tilapia feed. The ingredient blends were extruded using a laboratory-scale single screw extruder with varying screw speeds (100, 150, and 200 rpm) and extruder barrel temperatures (100, 125, and 150 oC). The resulting extrudates were subjected to extensive analyses of physical properties, which included unit density, bulk density, expansion ratio, moisture content, sinking velocity, color (L*, a*, and b*), water absorption, water solubility, and pellet durability indices. Several extruder parameters, including mass flow rate, moisture content at the die, net torque, specific mechanical energy, die pressure, and apparent viscosity were measured to quantify the extruder behavior during processing. Increasing the DDGS levels from 20 to 30% db, protein content from 30 to 35% db, feed moisture content from 25 to 45% db, and processing temperature from 100 to 150 oC significantly decreased the PDI values by 7.50, 16.2, 17.2, and 16.6%, respectively. Increasing the feed moisture content from 25 to 45% db resulted in a substantial increase in SME values by 256.2%. On the other hand,; increasing the screw speed from 100 to 200 rpm significantly decreased the SME values by 33.7%.