Tobacco and cannabis use pose major health risks and are major contributors to causes of death worldwide. Mobile phone-based cessation apps for these substances are gaining popularity, often used as a component of traditional interventions. This study aimed to analyze adherence to an intervention using a mobile phone application (App-therapy Prescind) as a function of sociodemographic variables (age, gender, educational level, and profession) as well as the primary activities supported by the app (reducing tobacco or cannabis use and increasing physical exercise). The participants were recruited through the web pages of the Occupational Risk Prevention Service and the Psychology Clinic of the University of Granada during the Covid-19 confinement period. The application’s content includes three components (self-report, motivational phrases, and goal-setting). Our findings indicate that being male, aged between 26 and 62, having a secondary or high school education, and being unemployed increase the likelihood of adherence to the Prescinde App-therapy three months after usage. Our findings highlight the importance of developing new therapeutic approaches and conducting in-depth studies on the factors associated with adherence to tobacco and cannabis cessation treatments via mobile phone applications.