Systems and methods for three-dimensional guidance and monitoring of a cryotherapy procedure, including virtually performing the procedure. A method of virtually performing a cryotherapy procedure includes: selecting a target object from three-dimensional image data displayed in three dimensions; selecting a three-dimensional ablation zone; selecting, from a library of virtual cryoprobe needles, a cryoprobe needle with a three-dimensional ablation zone that corresponds to the selected ablation zone; comparing the location of the target object with the selected ablation zone, the location of the ablation zone encompassing the target object to the greatest extent being an optimal location, determining, via a processor, a virtual trajectory for the virtual cryoprobe needle from an entry site to the target object when the ablation zone of the virtual cryoprobe needle is in the optimal position; and calculating a result of the procedure based on the target object, the selected ablation zone, the selected needle, and a duration of treatment. Guidance may also optionally be provided during an actual cryotherapy procedure, based upon three dimensional image data and/or data from one or more sensors, for example according to the results of the virtual cryotherapy procedure.