Most of the thermoduric organisms and their spores are capable of surviving pasteurization (75°C/15 s), and they can enter downstream processes. Combinations of high temperatures and short holding times (130–150°C/2–10 s) are effective strategies to reduce the levels of thermoduric bacteria. However, the intense application of heat often leads to over-processing, affecting quality and nutritional content. Strategies leading to reduce the impact of thermal processing have become a topic of industrial interest. A promising technology under development at our research group consists in combining the energy released by hydrodynamic cavitation with thermal treatment to reduce the levels of thermoduric sporeformers. This study summarizes our efforts in developing a continuous cavitation-assisted thermal treatment for the reduction of thermoduric sporeformers in skim milk concentrate (SMC). The experiments were conducted using a pilot scale cavitator coupled with a custom fabricated thermal unit. The SMC temperature in different processing steps was monitored during experiments. The increased in the temperature (delta T) due to cavitation increased with the SMC total solids (TS), yielding values of 31.35 ± 2.7, 35.15 ± 1.6, and 42.85 ± 1.4°C at 11, 25, and 36%, respectively. The experimental delta T data were modeled using a polynomial equation showing a satisfactory correlation (R² = 0.98). The microbial efficiency was evaluated in SMC (36% TS) inoculated with vegetative cells of Bacillus coagulans (ATCC 12245). The inoculated samples (4.67 ± 0.18 log) were treated by cavitation (60 Hz and 50 L h⁻¹), thermal treatment (75°C/15 s), and combined cavitation-thermal treatment. The 4.67 log of vegetative cell was reduced to 1.17 log by cavitation-thermal treatment, while thermal treatment reduced to 1.90 log. Contrary, individual cavitation did not produce any significant reduction. The outcomes of this study present opportunities for utilizing cavitation-assisted thermal treatment for inactivating thermoduric sporeformers and potentially the spores by a single pass.