The current study focuses on the engine performance and emission analysis of a 4 stroke compression ignition engine powered by medical waste plastic oil (WPO) followed by their optimization study and economic analysis. Engine tests were conducted using WPO blended diesel at various proportions to acquire required data for training the ANN model, which enables better prediction for the engine performance by making use of the standard back-propagation algorithm.Considering supervised data obtained from repeated engine tests, an arti cial intelligence-based model of ANN was designed to select different parameters of performance and emission as output layers, at the same time engine loading and different blending ratio of the test fuels were taken as the input layers. The ANN model was built up making use of 80% of testing outcomes for training. The ANN model forecasted engine performance and exhaust emission with regression coe cients (R) at 0.989-0.998 intervals and a mean relative error from 0.002% to 0.348%. Such results illustrated the effectiveness of the ANN model for estimating emissions and the performance of diesel engines. This study demonstrates the use of arti cial neural networks (ANNs) to forecast a multi-component fuel mixture, which is novel and reduces the amount of experimental effort required to determine the engine output characteristics. Moreover, the economic viability of the use of 20WPO as an alternative to diesel was justi ed by thermo-economic analysis.The Important Highlights Of The Work Are 1. Study of performance and emission diesel engine fuelled with WPO blended diesel. 2. Development of an arti cial intelligence-based ANN model at speci c engine conditions. 3. Analysis of productivity of ANN model developer for this experiment and test the economic feasibility.