Working with and treating individuals with co-occurring substance misuse presents unique challenges for mental health nurses. Substance misuse is common in mental health settings, and its clinical challenges with system barriers impede positive treatment outcomes. To work effectively in everyday clinical practice with dual diagnosis clients, nurses need to consider potential guiding principles. These principles pertain to treatment aims, engagement, assessment, symptoms, care plans, cycle of change, motivational interviewing, traps to avoid, active treatment, relapse prevention, agency collaboration, and treatment diversity. Clinical tools are easily accessible resources that can provide a framework for contemporary practice in a range of settings. Such resources are helpful in practice and as a foundation for orientation, education, self-reflection, and peer review. Setting expectations for everyday practice and ensuring that clients with a dual diagnosis receive the best care possible are important goals for the nursing profession.