Microwave-induced thermoacoustic imaging (MTAI) using low-energy and long-wavelength microwave photons has great potential in detecting deep-seated diseases due to its unique ability of visualizing intrinsic electric properties of tissue in high resolution. However, the low contrast in conductivity between a target (e.g., a tumor) and the surroundings sets a fundamental limit for achieving a high imaging sensitivity, which significantly hinders its biomedical applications. To overcome this limit, we develop a split ring resonator (SRR) topology based MTAI (SRR-MTAI) approach to achieve highly sensitive detection by precise manipulation and efficient delivery of microwave energy. The in vitro experiments show that SRR-MTAI demonstrates an ultrahigh sensitivity of distinguishing a 0.4% difference in saline concentrations and a 2.5-fold enhancement of detecting a tissue target which mimicks a tumor embedded at a depth of 2 cm. The in vivo animal experiments conducted indicate that the imaging sensitivity between a tumor and the surrounding tissue is increased by 3.3-fold using SRR-MTAI. The dramatic enhancement in imaging sensitivity suggests that SRR-MTAI has the potential to open new avenues for MTAI to tackle a variety of biomedical problems that were impossible previously.