BACKGROUND: Identifying individual and contextual factors that influence adolescent well-being is a research priority. This study aimed to assess the prevalence of symptoms of mental health problems and some related factors in Italian adolescents in 2017-2018. METHODS: The present study was a cross-sectional survey among 3002 students aged 15-16 years who resided in two Italian provinces, in North and South Italy. Symptoms of mental health problems were assessed using the SDQ and CES-DC, and students' risk-taking behaviors and school climate perception were assessed. All information was collected anonymously. Logistic regression models were used to assess the associations of tobacco and alcohol use, screen time, bullying, and school climate with symptoms of mental health problems. RESULTS: One student out of five reported symptoms of mental health problems, with a more than double proportion among girls than boys (28.7% vs 10.4% with depressive symptoms, respectively). Thirty percent and 40% of students smoked tobacco or drank alcoholic beverages at least once in the past month, and more than 40% reported being victims or authors of bullying in the past 6 months. Smoking behavior, alcohol consumption, screen time, bullying, and negative school climate had 1.2- to 3.3-fold increased odds of symptoms of mental health problems without substantial differences between sexes and geographical areas. CONCLUSIONS Tobacco and alcohol use, screen time, bullying, and school climate were independently associated with symptoms of mental health problems in a large sample of 15-16-year-old Italian adolescents without substantial gender and geographical differences.