Quantitative acoustic microscopy (QAM) is a cutting-edge imaging modality that leverages very high-frequency ultrasound to characterize the acoustic and mechanical properties of biological tissues at microscopic resolutions. Radio-frequency echo signals are digitized and processed to yield two-dimensional maps. This paper introduces a weighted Hankel-based spectral method with a reweighting strategy to enhance robustness with regard to noise and reduce unreliable acoustic parameter estimates. Additionally, we derive, for the first time in QAM, Cramér-Rao bounds to establish theoretical performance benchmarks for acoustic parameter estimation. Simulations and experimental results demonstrate that the proposed method consistently outperform standard autoregressive approach, particularly under challenging conditions. These advancements promise to improve the accuracy and reliability of tissue characterization, enhancing the potential of QAM for biomedical applications.