In ultrasonography, ultrasound contrast agents (UCAs) that possess high acoustic impedance mismatch with the bulk medium are frequently employed to highlight the borders between tissues by enhanced ultrasound scattering in a clinic. Typically, the most common UCA, microbubble, is generally close in size to a red blood cell (<∼10 μm). These microscale UCAs cannot be directly entrapped into the target cells but generate several orders of magnitude stronger echo signals than the nanoscale ones. And their large containment and high ultrasound responsiveness also greatly facilitate to perform combined treatments, e.g., drug delivery and other imaging techniques. So multifunctionalized microscale UCAs appear on this scene and keep growing toward a promising direction for precise theranostics. In this review, we systematically summarize the new advances in the principles and preparations of multifunctionalized microscale UCAs and their medical applications for malignant tumors.