Example systems, methods and apparatus to process medical prescription order rejections are disclosed. An example computer-implemented method, executed by one or more processors, to process a medical prescription order rejection, the method comprising submitting, using one or more processors, a first order for a medical prescription to a third-party entity for payment, when the first order is rejected by the third-party entity, processing, with a machine learning model, the first order to form a second order for the medical prescription, submitting, using one or more processors, the second order for the medical prescription to a third-party entity for payment, and when the second order is approved by the third-party entity, notifying, using one or more processors, a prescription fulfillment entity that the medical prescription is available to be fulfilled.