Introduction: The college years are characterized by psychosocial and biological phenomena that may impact mental health, such as heightened sensitivity to social stressors and compromises in sleep quantity and quality. The current study uses a biopsychosocial approach to examine the associations among interpersonal stress, Fear of Missing Out (FoMO), insomnia, and mental health. Methods: Survey data were collected from 283 undergraduate students (90% female) with a mean age of 21.4 years. A path analysis was utilized to test a mediational model linking interpersonal stress and FoMO with mental health through a mediator of insomnia. We hypothesized that higher levels of interpersonal stress and FoMO would be associated with higher levels of insomnia symptoms, which would in turn be associated with poorer mental health. Results: As predicted, insomnia partially mediated significant associations of interpersonal stress and FoMO with mental health. The association of interpersonal stress with insomnia and mental health was more robust than the association of FoMO with these variables. Conclusions: The pathway from interpersonal stress and/or FoMO, through insomnia, to compromises in mental health may be modifiable through behavioral interventions focusing on coping skills, sleep hygiene, and even technology-related habit changes. Recommendations to help disrupt this pathway, particularly among college students, are discussed.