Background: The growing burden of chronic illnesses calls for integrated and sustainable models of Primary Healthcare (PHC) that emphasize health promotion and patient-centered care. Interprofessional collaboration between General Practitioners (GPs) and Family and Community Nurses (FCNs) is a strategic approach to enhancing continuity of care and supporting individuals in adopting healthy behaviors across the trajectory of chronic conditions. This study aims to explore the experiences and perspectives of GPs and FCNs in Italy, with the goal of identifying the barriers, enablers, and transformative dynamics that can inform future PHC models. Methods: A qualitative study was conducted with four focus groups with 21 participants (8 GPs and 13 FCNs) from three Italian regions, carried out between March and November 2023. Data were analyzed using Reflexive Thematic Analysis (RTA) following Braun and Clarke's framework. Ethical approval was obtained from the University of Parma (Protocol No. 0266537-21 October 2022). Results: Four themes and sixteen subthemes were identified: (1) barriers to effective collaboration (role ambiguity, limited time, structural misalignments); (2) facilitators of collaboration (openness, mutual recognition, shared goals); (3) team-building processes (phases of trust development, shared values, reflective problem-solving); and (4) transformation of work practices (improved patient outcomes, flexible methodologies, integrated care strategies). Conclusions: Interprofessional collaboration between GPs and FCNs enhances the capacity of PHC to address the complex needs of people with chronic conditions. Aligning relational, organizational, and structural factors is essential for sustainable, health-promoting care models. Tailored training, protected time, and shared spaces are critical to foster teamwork, promote patient empowerment, and ensure continuity of care in chronic illness management.