About ten years prior to the events of Legion, she disappears from Stephen's life after teaching him how to control his condition, allowing him to usefully harness his aspects and prevent them from disappearing. She somehow understands his abilities better than Stephen himself does. After she disappears, Stephen devotes a great deal of effort to finding her, but to little avail. Not much is explicitly shown of their relationship, but he considers her beautiful and has affection for her, so it is possible that they are romantically involved before she leaves.
In Legion, Monica entices Stephen into working for her by showing him a picture of Sandra, taken with a camera that shows pictures of the past; the picture indicates that, ten years ago, she took a train to New York, providing Stephen with the first solid clue to her whereabouts he has found in years.