The yield and higher heating value (HHV) of bio-oil products are significant performance parameters for the hydrothermal conversion of high-water and high-lipid biomass. Machine learning (ML) modeling prediction is a fast and convenient means of obtaining performance parameters. An informative dataset with 243 samples was prepared, and two highly adapted ML algorithms were used: Random Forest (RF) and Extreme Gradient Boosting Tree (XGBoost). It is interesting to note that the developed ML models demonstrated great prediction ability; for example, the regression coefficient () of the XGBoost model for yield and HHV prediction was as high as 0.942 and 0.940, respectively. Furthermore, partial dependence plots and SHAP (SHapley Additive exPlanations) interpretability methodologies were adopted to address the main contributions of the feature identification and response behavior analysis of the features. The results demonstrated that the biomass composition had the greatest effect on bio-oil yield, with fat contributing up to 40%. In contrast, the elemental composition had the most significant effect on the HHV of bio-oil. Notably, hydrogen content affected the HHV of up to 4.5 units. The interaction response behavior showed that the interaction of the process parameters with feedstock properties was most common and significant. The information obtained from the response mechanism can be used to enhance the subsequent hydrothermal fuel preparation process for bio-oils.