Ultrasonic microneedle patches, a class of ultrasound-driven transdermal drug delivery systems, are promising in addressing bacterial biofilms. This device has been proven to be more effective in treating Staphylococcus aureus biofilms than drug in free solution. However, there exists a notable gap in understanding how various excitation conditions and material parameters affect drug delivery efficiency. This study aims to fill this void by conducting an comprehensive multi-physics numerical analysis of ultrasonic microneedle patches, with the ultimate goal of enhancing drug delivery. First, we investigate the impact of various ultrasound frequencies on drug penetration depths. The findings reveal that local resonance can accelerate drug release within a shorter time window (first 1.5 h), whereas non-resonant frequencies enable more profound and prolonged diffusion. This information is crucial for medical professionals in selecting the most effective frequency for optimal drug administration. Furthermore, our investigation extends to the effects of applied voltage on temperature distribution, a critical aspect for ensuring medical safety during the application of these patches. Additionally, we examine how particles of different sizes respond to acoustic pressure and streaming fields, providing valuable insights for tailoring drug delivery strategies to specific therapeutic needs. Overall, our findings offer comprehensive guidelines for the effective use of ultrasonic microneedle patches, potentially shifting the paradigm in patient care and enhancing the overall quality of life.