The thermosonication processing has been evaluated as a smart alternative to overcoming the heat treatment limitations associated with longer holding times at high temperatures. In this regard, this innovative technique combines acoustic energy with moderate heat treatments to inactivate pathogenic and spoilage microorganisms and endogenous enzymes in foods and beverages. Thermosonication treatment employs short holding times, which can promote the maintenance of phytochemical compounds and sensory characteristics of food products. The challenges and advantages of this emerging technology were reviewed in contrast to conventional heat treatments. Additionally, the process design of ultrasound combined with mild thermal treatments was discussed. Thermosonication is presented as a promising technique to inactivate microorganisms and enzymes. Also, it has not affected the nutritional and sensory quality of different food products. However, thermosonication treatments must be standardized. Some studies used only acoustic cavitation as a source of heat. Furthermore, many studies did not calculate or present the actual thermal energy provided by thermosonication processes. Therefore, temperature monitoring throughout thermosonication processing is crucial to ensure the suitable process design, avoiding the negative impacts observed in thermally treated products, such as degradation of bioactive compounds and off-flavors formation.