Cancer care is multifactorial and patient centered. It can be described as a complex package of interventions, delivered at different times and places with different intentions, which interacts and cannot be evaluated in isolation. The authors discuss the evolving nature of cancer care and address the challenges faced by biomedical research methodology when applied to cancer care. In addition, they identify new research directions to meet these challenges. These include qualitative research, mixed methods research, and approaches based on systems thinking.