To maximize energy recovery in waste-to-energy (WTE) systems, the High Heating Value (HHV) of municipal solid waste (MSW) must be accurately estimated. To forecast the HHV of MSW, this study proposes a unique method that combines an Artificial Neural Network (ANN) model with Latin Hypercube Sampling (LHS), with a focus on Solan City, Himachal Pradesh, India. In the present study, the elemental characteristics of waste have been used to deal with uncertainty and to find the suitable parameters responsible for the HHV of the MSW. Initially, Latin Hypercube Sampling (LHS) has been used to deal with uncertainty in the elemental composition of MSW, which includes carbon (C), hydrogen (H), nitrogen (N), sulfur (S), and oxygen (O) content. This elemental composition has been used as input parameters to the ANN model for predicting the HHV of MSW. The network 5-28-5-1 offered a minimum MAPE value of 2.18%, MSE, RMSE and R2 values are 0.012, 0.107 and 0.767, respectively. Thereafter, a synaptic weight approach was used to find the most significant parameters responsible for HHV in MSW. It was observed that carbon is the most suitable parameter for HHV of MSW. By dealing with the uncertainty in MSW characteristics, the integration of LHS strengthens the robustness of the model. The results offer an accurate and economical approach for HHV estimation, which will be useful for improving the MSW management and WTE conversion procedures.