Insomnia and major depression frequently co-occur, with approximately 59% of patients meeting diagnostic criteria for depression also reporting symptoms of insomnia. Although disorder-specific protocols target the treatment of each condition independently, their concurrent presentation complicates treatment selection and deployment. In this chapter, we discuss how mindfulness-based interventions can be leveraged to address these comorbid presentations through three key transdiagnostic mechanisms: cognitive control, emotion regulation, and body awareness. We introduce the Mindfulness Case Conceptualization framework, explicitly designed to bridge mindfulness research and clinical practice for patients presenting with complex, comorbid issues. Using this framework, we illustrate how Mindfulness-Based Treatment for Insomnia (MBTI) can be intentionally deployed to simultaneously address insomnia and depression, supported by three detailed, illustrative case examples. The goal of this chapter is to provide clinicians a practical roadmap for personalizing mindfulness-based interventions to target core transdiagnostic processes underlying these conditions.