Systems and methods generate a segmentation network for image segmentation using global optimization. A method for automatic generation of at least one segmentation network includes providing an initial set of hyperparameters to construct a segmentation network. The hyperparameters define operations for a set of block structures and connections between the block structures. The segmentation network is trained using a first set of images with ground truth. An objective function value for the trained segmentation network is generated using a second set of images having ground truth. Generating the objective function includes setting the objective function to a predetermined value responsive to identifying an untrainable condition of the trained initial segmentation network. The set of hyperparameters is updated by performing an optimization algorithm on the objective function value to construct an updated segmentation network. The training of the segmentation network, the generating of the objective function, and the updating of the set of hyperparameters for the updated segmentation network are iterated to generate a network architecture for the segmentation network.