Systems and methods for providing an optimal treatment plan for delivering a prescribed radiation dose to a predefined target volume within a patient using an external beam radiation delivery unit are provided. The systems have an interface which is adapted to receive information related to a prescribed radiation dose, a predefined target volume within a patient, and parameters associated with an external beam delivery unit. The systems also have a treatment plan modeling processor which is adapted to receive all of the input data and develop a treatment plan optimization model defining a global system. The systems also have an optimization processor which is adapted to determine an optimal treatment plan based on the treatment plan optimization model and all the input data.