Pretreatments of pH and heat with zero-valent iron (ZVI) additions enhance anaerobic digestion and increase reducing sugar availability for optimum biogas production. This study aimed to optimize the conditions of different pH and heat pretreatment with additional ZVI to yield higher biogas amounts from the anaerobic digestion (AD) of cassava wastewater. Thirteen pH conditions, ten ZVI concentrations, and eleven heating periods were varied and measured to optimize the standard conditions. Four mathematical models that are widely used to evaluate the cumulative biogas production were employed, namely, the Modified Gompertz, Logistic, Transference, and Exponential models. The pretreatment of pH 10 and 35 min of boiling time with a ZVI concentration of 60 g·kg·TVS−1 produced the highest cumulative biogas at the end of the AD process. The Logistic and Modified Gompertz models were better fitted with the experimental data than the other models. Interestingly, the optimized conditions altered the biogas production rate but prolonged the lag phase. A reasonably positive correlation was also found between the FeOOH amount and biogas production rate in the LF and MG models. These optimal fitted models, kinetics parameters, and possible correlations are novel findings that can help develop extensive scale developments for biogas generation from cassava wastewater.