In this research article, a Python-based machine learning model prediction study was conducted based on the study results obtained from sudden expansion tubes containing different expansion angles, dimpled fin structures and nanofluids, whose thermo-hydraulic performance was previously examined. In the study, Artificial Neural Network and Ridge regression models were used to make predictions on the average Nusselt number (Nu), average Darcy friction factor (f) and performance evaluation criteria (PEC). Physical variations of the sudden expansion tube were taken into account and a detailed comparison of the results was made. A superior average Nu was acquired as 172.45 %, 22.05 %, 17.18 %, 13.65 %, and 7.76 % compared to Ag-MgO/H2O, Al2O3/H2O (blade), CoFe2O4/H2O, Al2O3/H2O (cylindrical), and Al2O3/H2O (platelet), respectively. The highest Performance Evaluation Criteria (PEC) for Re= 2000 based on Al2O3/H2O (platelet) shows an increase of 4.84 %, 12.08 %, 11.76 %, 66.05 %, and 148.94 % compared to Al2O3/H2O (cylindrical), Al2O3/H2O (blade), CoFe2O4/H2O, Fe3O4/H2O, and Ag-MgO/H2O, respectively. From the results obtained, it was determined that Python-based Machine Learning approach which facilitates custom optimizations showed a significant performance with small margins of error in predicting the heat transfer parameters. The lowest error rates of machine learning and polynomial ridge regression models ranged from 0.2 % to 5.4 % for the unseen test set and the application of Python-based algorithms provided considerable savings in calculation time compared to conventional methods. On the other hand, using machine learning models with feature engineering has been found to increase model performance by at least 30 %. In these years when studies on the predictions of thermo-hydraulic studies are very rare in the literature, this study is intended to facilitate scientists, engineers and academicians who will further study on this subject.