Anaerobic digestion of sugarcane straw co-digested with sugarcane filter cake was investigated with a special focus on macronutrients supplementation for an optimized conversion process. Experimental data from batch tests and a semi-continuous experiment operated in different supplementation phases were used for modeling the conversion kinetics based on continuous stirred-tank reactors. The semi-continuous experiment showed an overall decrease in the performance along the inoculum washout from the reactors. By supplementing nitrogen alone or in combination to phosphorus and sulfur the specific methane production significantly increased (P < 0.05) by 17% and 44%, respectively. Although the two-pool one-step model has fitted well to the batch experimental data (R-2 > 0.99), the use of the depicted kinetics did not provide a good estimation for process simulation of the semi-continuous process (in any supplementation phase), possibly due to the different feeding modes and inoculum source, activity and adaptation.