The study evaluated anaerobic co-digestion of poultry dropping and pawpaw peels and the optimization of important process parameters. The physic-chemical analyses of the substrates were done using standard methods after application of mechanical, thermal and chemical pre-treatments methods. Gas chromatography analysis revealed the gas composition to be within the range of 66-68% methane and 18-23% carbon dioxide. The study equally revealed that combination of the different pre-treatment methods enhanced enormous biogas yield from the digestion. Optimization of the generated biogas data were carried out using the Response Surface Methodology and the Artificial Neural Networks. The coefficient of determination ( R-2) for RSM ( 0.9181) was lower compare to that of ANN ( 0.9828). This shows that ANN model gives higher accuracy than RSM model for the current. Further usage of Carica papaya peels for biogas generation is advocated. (C) 2016 The Authors. Published by Elsevier Ltd.