Background: Individuals with multimorbidity and complexity have multifaceted care needs requiring integrated and collaborative care from nurses, families, and health care teams. Nurses, as the frontline care professionals, should develop therapeutic relationships with patients and their families and professional relationships with health care team members to ensure the delivery of effective integrated care. Failure to develop effective interpersonal and professional relationships can negatively affect patient care. Objective: The purpose of this study was to explore nurses’ challenges with developing interpersonal and professional relationships during integrated care for individuals with multimorbidity and complexity. Methods: A descriptive qualitative design was used. We interviewed a purposive sample of 19 nurses with experience of caring for individuals with multimorbidity and complexity across two hospitals in Pakistan. Semi-structured interviews were used for data collection, and data were analyzed using reflexive thematic analysis. Results: Two challenges were identified affecting the relationships between patients’ families and nurses, and two challenges influencing the professional relationships within the team. Families withheld information, controlled care access of their relatives, posed unrealistic demands, and abused nurses, affecting nurse-family relationships. Power struggles to demonstrate authority in decision-making were common within health care teams, affecting nurses’ professional capacity to provide effective care. Conclusions: Health care team, patient, and family collaboration is instrumental in improved care for individuals with multimorbidity and complexity. Nurse leaders and health care organizations should take initiatives to address nurses’ interpersonal confrontations to support them in the provision of quality care.