Implementation science plays a vital role in the advancement of cancer care via the application of methods that facilitate the integration of evidence-based interventions into real-world healthcare settings. A diverse and expanding body of primary implementation research in cancer care now exists, that aims to enhance the quality and experience of care for people living with cancer, their caregivers, and healthcare teams. Efforts to consolidate the available literature in this space has resulted in a proliferation of systematic reviews, yet review teams commonly face specific challenges when identifying, appraising, and synthesising primary implementation research. To enhance the strength and applicability of review findings and optimise cancer care, we describe five key challenges unique to systematic reviews of primary implementation research. These challenges include (1) descriptors used in implementation science publications, (2) distinction between evidence-based interventions and implementation strategies, (3) assessment of external validity, (4) synthesis of implementation studies with substantial clinical and methodological diversity, and (5) variability in defining implementation ‘success’. We outline possible solutions and highlight resources that can be used by authors of primary implementation research, as well as systematic review and editorial teams to address the identified challenges.