Systems and methods for processing tissue samples using acoustic energy. The tissue sample may be collected and placed on a substrate (e.g., microscope slide), or other sample holder. A transfer substrate may be positioned on the other side of the sample opposite the substrate. A microscope incorporated with the acoustic treatment system may be used to view, identify and select a portion of the sample to be transferred from the initial substrate to the transfer substrate. The selected portion of the sample is exposed to focused acoustic energy while disposed between the two substrates. The focused acoustic energy has characteristics (e.g., high frequency, small focal zone) that may be effective to transfer the selected portion of the sample from the initial substrate to the transfer substrate. Such transfer may occur with little to no damage to the sample, for example, at low temperature isothermal conditions and/or little to no cavitation of or around the sample.