High-intensity focused ultrasound (HIFU) enables localized ablation of biological tissues by capitalizing on the synergistic effects of heating and cavitation. Monitoring of those effects is essential for improving the efficacy and safety of HIFU interventions. Herein, we suggest a hybrid optoacoustic-ultrasound (OPUS) approach for real-time assessment of heating and cavitation processes while providing an essential anatomical reference for accurate localization of the HIFU-induced lesion. Both effects could clearly be observed by exploiting the temperature dependence of optoacoustic (OA) signals and the strong contrast of gas bubbles in pulse-echo ultrasound (US) images. The differences in temperature increase and its rate, as recorded with a thermal camera for different HIFU pressures, evinced the onset of cavitation at the expected pressure threshold. The estimated temperatures based on OA signal variations were also within 10–20 % agreement with the camera readings for temperatures below the coagulation threshold (∼50 °C). Experiments performed in excised tissues as well as in apost-mortemmouse demonstrate that both heating and cavitation effects can be effectively visualized and tracked using the OPUS approach. The good sensitivity of the suggested method for HIFU monitoring purposes was manifested by a significant increase in contrast-to-noise ratio within the ablated region by > 10 dB and > 5 dB for the OA and US images, respectively. The hybrid OPUS-based monitoring approach offers the ease of handheld operation thus can readily be implemented in a bedside setting to benefit several types of HIFU treatments used in the clinics.