Systems and methods related to learning-based analyzers (both supervised and unsupervised) for mitigating latch-up in integrated circuits are provided. An example method includes obtaining latch-up data concerning at least one integrated circuit configured to operate under a range of temperature conditions, where the at least one integrated circuit comprises a core portion including at least a plurality of devices each having one or more structural features formed using a lithographic process, and an input/output portion. The method further includes training the learning-based system based on training data derived from the latch-up data and a first layout rule concerning a first spacing between the core portion and the input/output portion. The method further includes using the learning-based system generating a second layout rule concerning the first spacing between the core portion and the input/output portion, where the second layout rule is different from the first layout rule.