Effective crop monitoring and accurate yield estimation are fundamental for informed decision-making in agricultural management. In this context, the present research focuses on estimating wheat yield in Nepal at the district level by combining Sentinel-3 SLSTR imagery with soil data and topographic features. Due to Nepal’s high-relief terrain, its districts exhibit diverse geographic and soil properties, leading to a wide range of yields, which poses challenges for modeling efforts. In light of this, we evaluated the performance of two machine learning algorithms, namely, the gradient boosting machine (GBM) and the extreme gradient boosting (XGBoost). The results demonstrated the superiority of the XGBoost-based model, achieving a determination coefficient (R2) of 0.89 and an RMSE of 0.3 t/ha for training, with an R2 of 0.61 and an RMSE of 0.42 t/ha for testing. The calibrated model improved the overall accuracy of yield estimates by up to 10% compared to GBM. Notably, total nitrogen content, slope, total column water vapor (TCWV), organic matter, and fractional vegetation cover (FVC) significantly influenced the predicted values. This study highlights the effectiveness of combining multi-source data and Sentinel-3 SLSTR, particularly proposing XGBoost as an alternative tool for accurately estimating yield at lower costs. Consequently, the findings suggest comprehensive and robust estimation models for spatially explicit yield forecasting and near-future yield projection using satellite data acquired two months before harvest. Future work can focus on assessing the suitability of agronomic practices in the region, thereby contributing to the early detection of yield anomalies and ensuring food security at the national level.