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High tumor interstitial fluid pressure (TIFP) is characteristic of solid tumors. Elevated TIFP inhibits the assimilation of macromolecular therapeutics in tumor tissue as well as it induces mechanical strain triggering cell proliferation in solid tumors. Common solid epithelial tumors of A431 carcinoma cells exhibit a TIFP of about 10–15 mmHg measured conventionally through wick-in-needle technique. A new scheme to determine topography and acoustic impedance in solid tumor is proposed through scanning acoustic microscopy. The change in amplitude and time of flight at 30 MHz acoustic signal is used to quantify the growth pattern and to calibrate elevation of TIFP. The wide variability of amplitude and frequency in topographic sections indicate discrete envelopes of individual tumors with localized TIFP. Further investigations in applying this non-invasive method as a means of measuring TIFP in subcutaneous mice xenograft tumors in situ could also enhance understanding of tumor microenvironment and vessel architecture in living tissue.