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The objective of this study was to determine the optimal thermoultrasound processing conditions for jackfruit nectar by applying response surface methodology and comparing the physicochemical parameters, antioxidant properties, microbiology, and fatty acid profile with pasteurized jackfruit nectar. Optimal condition was 80% of amplitude at 45 ± 1°C for 20 ± 1 min, allowing physical stability of 68%, 60% of pectin methylesterase activity, ascorbic acid of 420 mg AA/L, total phenolic of 134 mg GAE/L, ABTS, DPPH, and chelating activity of 3,510 µmol TE/L, 75 µmol TE/L, and 96%, respectively. The thermoultrasonicated jackfruit nectar had lower microbial load and higher total soluble solids, ascorbic acid content, total phenolic content, antioxidant activity than pasteurized, and similar unsaturated fatty acids to the untreated sample. Our results demonstrated that thermoultrasound could be an option for processing jackfruit nectar as an alternative to pasteurization that allows successful inactivation of microorganisms, inactivation of enzymes, and good quality parameters. Practical applications: Based on consumer demand for more natural or fresh‐like products, alternative technologies have been evaluated by research works looking to reduce the effects of heat treatments in the Food Industry. Among these technologies, thermoultrasound technology have gained relevance and seems to be a good replacement to inactivate microorganisms and enzymes without affecting the quality parameters, maintaining the unsaturated fatty acids content, and even increasing bioactive compounds. For example, the thermoultrasound application in jackfruit nectar has been demonstrated as a viable preservation technique to develop an innocuous nectar without affecting their food quality. Nevertheless, in order to solve the challenges about potential applications of ultrasound technology, further research is needed to obtain optimal processing conditions according to the food matrix quality required. [ABSTRACT FROM AUTHOR]