We propose an integrated approach to optimize lithography-generated guide structures for the directed self-assembly (DSA) of block co-polymers. Modeling the entire lithography/DSA co-process, little a priori knowledge is required, and well-performing solutions can be obtained quasi-automatically. To maintain a feasible optimization runtime, a reduced DSA model is employed. Predictivity and stability are ensured by the introduction of a self-adaptive calibration and model correction routine, for which a more exact phase-field DSA model is used. By an application to a via multiplication example, the feasibility and the potentials of the approach are demonstrated and discussed