The study focuses on developing a comprehensive design approach for a flow-through ultrasonic reactor (sonicator) to tackle challenges like low energy transfer efficiency and unstable system performance. The simulation accounts for structural vibrations, structural-fluid interactions, and pressure distributions within the cavitation zone under single-frequency excitation. Different geometrical designs of cylindrical sonicators are analyzed, with input parameters tailored to acquire higher acoustic cavitation intensity. The findings reveal a novel hexagonal ring-shaped excitation structure that reduces coupling losses, ensures uniform acoustic pressure distribution, and generates symmetric vibration mode shapes. The study emphasizes the separation of parasitic modes from the desired resonance frequency response and simulates the influence of bubbly liquid properties through complex wave numbers and harmonic responses. Experimental validation on a manufactured prototype, including mechanical and electrical impedance, sound pressure spectrum, and cavitation intensity, supports the simulated results. Ultimately, the sonicator exhibits three feasible resonance frequencies to be used pairwise at the certain temperature and input power interval for different applications.