Abstract: A method is provided for interactive treatment planning of IMRT or other radiation modalities that employs non-uniform tuning or optimization. One aspect provides a voxel-dependent penalty scheme by varying the importance factor associated with a voxel, the prescription at the voxel, or the form of the penalty function at the voxel in a non-uniform manner. Another aspect provides the dose shape at a specified sub-volume tuned by varying the local importance factor(s) or the local prescription or the form/value of penalty function. Yet another aspect provides the use of a non-uniform penalty scheme (non-uniform importance factors, non-uniform prescription in one or more structures, or non-uniform form of the objective function). Still another aspect provides the method of pre-estimating the values of the voxel-specific importance factors using prior dosimetric knowledge of a given system.