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. One such method comprises: receiving information corresponding to at least one parameter related to intensity-modulated radiation therapy (IMRT) to be used in developing the optimal treatment plan; receiving information corresponding to at least one clinical objective related to a target volume and a critical structure; developing a treatment plan optimization model based on a plurality of variables corresponding to the at least one parameter related to IMRT and the at least one clinical objective which define a global system; and developing a globally optimal treatment plan which optimizes the at least one clinical objective subject to the at least one parameter.