Introduction: Healthcare professionals working with individuals who have experienced trauma are at risk of experiencing secondary trauma. Purpose: To explore the perspectives and experiences of addiction nurses working in substitution treatment units and harm reduction services regarding the physical or psychological trauma of individuals coping with the dual burden of addiction and trauma. Methodology: A mixed-method study (quantitative and qualitative) involving 111 addiction nurses. For the collection of quantitative data, the Greek version of the Professional Quality of Life Scale was used, which assesses compassion satisfaction, professional burnout, and secondary traumatic stress, as well as a questionnaire capturing demographic, individual, and professional characteristics. Eight nurses participated in semistructured interviews. Results: The majority of participants reported (96.4%) moderate to high levels of compassion satisfaction while more than half (54.4%) of the participants reported low levels of professional burnout, and about half (49.5%) reported low levels of secondary traumatic stress. Considering Stamm’s interpretation of the triad of high compassion satisfaction, moderate-to-low professional burnout, and secondary traumatic stress, the results of this study fall into the positive results category. Good physical health, participants’ readiness to care for individuals with trauma, high levels of cooperation, respect for teamwork, positive work climate, and seamless colleague support were positively related to higher levels of compassion satisfaction. Conclusions: Recognizing, reflecting on, and understanding trauma processes protected participants from mirroring the helplessness, frustration, and feelings of incompetence they encountered on the trauma responses of the individuals and families they cared for.