Implementation of evidence-based cancer prevention and early detection in low- and middle-income countries (LMIC) is challenging. Limited and inappropriate introduction of novel alternatives results in an equity gap whereby low-income populations receive a lower benefit. Implementation research represents an opportunity to foster the adoption and expansion of evidence-based cancer control strategies; however, scientific development in high-income countries does not necessarily fulfill the particular needs of LMIC in the field. A review on the link between implementation research and practice, the tension between theory and pragmatism, the conflict around implementation research methods, and determinants of research priority definition was carried out by considering the perspective of cancer prevention and early detection implementers in LMIC. Basic principles and alternatives to overcome implementation research challenges in these settings are discussed.