This study explored the effect of thermosonication on the nutritional properties of lapsi (Choerospondias axillaris) fruit juice. The intent of the present investigation was to process lapsi fruit juice using both thermosonication and thermal pasteurisation and to compare the effects of these treatments on the juice's physicochemical, nutritional, and microbiological qualities. In order to maximise the retention of nutritional properties, enhance juice quality, and boost efficiency, an artificial neural network (ANN) model was also developed to forecast the optimisation of process parameters for the quality of lapsi fruit juice. This study establishes a novel experimental planning method using an ANN to multi-objectively optimise the extraction process and identify the ideal extraction conditions for thermosonication (50, 75, and 100% amplitude at 30, 40, and 50 °C for 15, 30, 45, and 60 min) to augment lapsi juice's nutritional and microbiological properties by improving certain attributes such as ascorbic acid (AA), antioxidant activity (AOA), total phenolic content (TPC), total flavonoid content (TFC), total plate count, and yeast and mould count (YMC). The maximum values for AA (71.80 ± 0.05 mg/100 mL), AOA (74.60 ± 0.28%), TPC (187.33 ± 0.03 mg gallic acid equivalents [GAE]/mL), TFC (127.27 ± 0.05 mg quercetin equivalents [QE]/mL), total plate count (not detected), and YMC were achieved in thermosonicated lapsi juice (TSLJ) under optimal conditions. For AA and TFC, the optimal conditions were 100% amplitude, 40 °C, and 45 min. For AOA and TPC, the optimal conditions were 100% amplitude, 40 °C, and 60 min, and for YMC, the optimal conditions were 100% amplitude, 50 °C, and 60 min. According to the findings, thermosonicated juices have improved nutritional properties, making them an excellent source of bioactive elements for use in both the food and pharmaceutical sectors. According to this study, ANN has been identified as a valuable tool for predicting the effectiveness of lapsi fruit juice extraction, and the application of thermosonication as an approach for lapsi juice preservation could be a potential successor to thermal pasteurisation. This approach can help to minimise or hinder quality degradation while improving the juice's functionality.