The relationship between substance use and mental health is complex, and both constitute a global public health burden. In the UK, the estimated annual financial costs of alcohol-related harm and illicit drug use are GBP 21.5 billion and GBP 10.7 billion, respectively. This issue is magnified in the North East of England, where treatment access is low and a large proportion of individuals experience socioeconomic deprivation. The present study aimed to explore the experiences of adults and adolescents accessing a substance misuse treatment service in the North East, in order to inform policy makers, commissioners, and providers of substance misuse treatment and prevention. Semi-structured qualitative interviews were conducted with an opportunistic sample of n = 15 adult participants (aged 18 years and over) and n = 10 adolescent participants (aged between 13 and 17 years). Interviews were audio-recorded, transcribed, anonymised, and analysed thematically. Five key themes were identified: (1) initiation of substance use, (2) early life experiences, (3) the bi-directional relationship of mental health and substance use, (4) cessation of substance use, and (5) accessing treatment. Future preventative interventions should focus on providing support to individuals who have been exposed to adverse childhood experiences, with treatment provision for individuals experiencing co-occurring mental health and substance use issues taking a more holistic approach.