Stress disrupts physiological and emotional homeostasis and therefore represents a risk factor for mental health difficulties. According to the diathesis-stress model, exposure to stress interacts with individual vulnerability factors (e.g., genetic or cognitive predisposition) to explain the risk of mental health difficulties. People with neurodevelopmental disorders, including autism (or “autism spectrum disorder”) and 22q11.2 deletion syndrome (22q11DS), are particularly vulnerable to stress and its negative effects. Exposure to major and/or repetitive stress during development can sensitize these individuals to subsequent stressors, through more intense physiological and affective responses to stress, ultimately leading to permanent changes (i.e., stress sensitization). The main aim of this thesis was to better understand the physiological (i.e., stress axis functioning) and affective (i.e., daily affective dynamics) processes underlying stress-related mental health difficulties in adolescents and young adults with autism and 22q11DS.