Vortex-based microfluidics has received significant attention for its unique characteristics of high efficiency, flexible control, and label-free properties for the past decades. Herein, we present a vortex-based acousto-inertial chip that allows both fluid and particle manipulation within a significantly wider flow range and lower excitation voltage. Composed of contraction−expansion array structures and vibrating microstructures combined with bubbles and sharp edges, such a configuration results in more vigorous vortical fluid motions. The overall improvement in device performance comes from the synergistic effect of acoustics and inertia, as well as the positive feedback loop formed by vibrating bubbles and sharp edges. We characterize flow patterns in the microchannels by fluorescence particle tracer experiments and uncover single-and double-vortex modes over a range of sample flow rates and excitation voltages. On this basis, the ability of rapid and efficient sample homogenization up to a flow rate of 200 μL/min under an excitation voltage of 15 V pp is verified by a two-fluid fluorescence mixing experiment. Moreover, the recirculation motion of particles in microvortices is investigated by using a high-speed imaging system. We also quantitatively measure the particle velocity variation on the trajectory and illustrate the capturing mechanism, which results from the interaction of the microvortices, particle dynamics, and composite microstructure perturbations. Further utilizing the shear forces derived by microvortices, our acousto-inertial chip is demonstrated to lysis red blood cells (RBCs) in a continuous, reagent-free manner. The high controllability and multifunction of this technology allow for the development of multistep miniaturized "lab-on-chip" analytical systems, which could significantly broaden the application of microvortex technology in biological, chemical, and clinical applications.