Nigerian gay, bisexual, and other men who have sex with men (GBMSM) experience social marginalisation, discrimination and violence due to their sexual orientation and same-sex attraction, which may affect mental health, substance use, and HIV sexual risk behavior. The goal of the current study was to conduct formative qualitative research to gain better understanding of these issues among GBMSM in Lagos, Nigeria. Face-to-face, semi-structured, in-depth interviews were conducted with 30 GBMSM in Lagos, Nigeria. Data were analysed using a deductive content analysis approach. We found that Nigerian GBMSM experienced both general life stressors as well as proximal and distal sexual minority identity stressors, including rejection by family members, harassment, and physical violence perpetrated by the general public and police officers. Participants described dealing with mental health problems within the context of family rejection, experienced stigma due to sexual orientation, and feelings of social isolation. Substance use was described as occurring within the context of social settings. Lastly, some participants mentioned that they engaged in risky sexual behaviour while under the influence of alcohol and drugs. These findings call for comprehensive and innovative, GBMSM-affirming behavioural healthcare, substance cessation services, and innovative HIV prevention interventions specifically designed and tailored for Nigerian GBMSM.