The objective of this decision support synthesis was to identify and review published and grey literature and to conduct stakeholder interviews to (1) describe the distinguishing characteristics of clinical nurse specialist (CNS) and nurse practitioner (NP) role definitions and competencies relevant to Canadian contexts, (2) identify the key barriers and facilitators for the effective development and utilization of CNS and NP roles and (3) inform the development of evidence-based recommendations for the individual, organizational and system supports required to better integrate CNS and NP roles into the Canadian healthcare system and advance the delivery of nursing and patient care services in Canada. Four types of advanced practice nurses (APNs) were the focus: CNSs, primary healthcare nurse practitioners (PHCNPs), acute care nurse practitioners (ACNPs) and a blended CNS/NP role. We worked with a multidisciplinary, multijurisdictional advisory board that helped identify documents and key informant interviewees, develop interview questions and formulate implications from our findings. We included 468 published and unpublished English- and French-language papers in a scoping review of the literature. We conducted interviews in English and French with 62 Canadian and international key informants (APNs, healthcare administrators, policy makers, nursing regulators, educators, physicians and other team members). We conducted four focus groups with a total of 19 APNs, educators, administrators and policy makers. A multidisciplinary roundtable convened by the Canadian Health Services Research Foundation formulated evidence-informed policy and practice recommendations based on the synthesis findings. This paper forms the foundation for this special issue, which contains 10 papers summarizing different dimensions of our synthesis. Here, we summarize the synthesis methods and the recommendations formulated at the roundtable.