<p>Substance use is more prevalent among people of sexual minorities than among heterosexual people. Additional factors, such as having experienced higher rates of violence, may contribute to increased health risks and thereby exacerbate health inequalities among these individuals. Therefore, this study aimed to assess the association between different socioeconomic factors, sexual orientation, and having experienced sexual violence, with hazardous drinking and hazardous cannabis use in university students, considering gender. We carried out a cross-sectional study in a sample of university students from the UManresa Campus of the Universitat de Vic—Universitat Central de Catalunya (Catalonia), during the 2021/2022 academic year, within the framework of the DESK-University project (n = 950). A total of 35.6% (n = 338) of the sample identified as boys and 64.4% (n = 612) as girls. In our study, we found that having experienced sexual violence with penetration (_adjusted PR = 1.9, 95% CI [1.4, 2.7]) was associated with hazardous drinking in boys. In girls, hazardous drinking was associated with identifying as lesbian (_adjusted PR = 1.9, 95% CI [1.2, 2.7]) and with having experienced sexual violence with physical contact (_adjusted PR = 1.3, 95% CI (1.0, 1.7)]). Hazardous cannabis use was associated with having experienced sexual violence without physical contact in boys (_adjusted PR = 3.4, 95% CI [1.1, 10.8]) and reporting a non-heterosexual orientation, especially in lesbian university students (_adjusted PR = 9.9, 95% CI [1.6, 60.6]). Incorporating a gender perspective and recognizing affective-sexual diversity in health programs and public policies are essential steps toward removing barriers and reducing inequalities, ultimately leading to better health outcomes for young people.</p>