The rising prevalence of noncommunicable diseases globally, with a strikingly disproportionate increase in prevalence and related mortality in low- and middle-income countries (LMICs), is a major threat to sustainable development. The epidemiologic trend of cancers in LMICs is of particular concern. Despite a lower incidence of cancer in LMICs compared with high-income countries, total cancer-related mortality is significantly higher in LMICs, especially in people younger than 65 years of age. The enormous economic impact of premature mortality and lost productive life years highlights the critical importance of galvanizing cancer prevention and management to achieve sustainable development. The rising burden of cancer in LMICs stresses an already weak health care and economic infrastructure and poses unique challenges. Although the WHO acknowledges that the effective management of cancer relies on early detection, accurate diagnosis, and access to appropriate multimodal therapy, the placement of priority on early detection cannot be assumed to be effective in LMICs, where limited downstream resources may be overwhelmed by the inevitable increases in number of diagnoses. This review discusses several factors and considerations that may compromise the success of cancer control programs in LMICs, particularly if the focus is only on early detection through screening and surveillance. It is intended to guide optimal implementation of cancer control programs by accentuating challenges common in LMICs and by emphasizing the importance of cancer prevention where relevant so that communities and stakeholders can work together to devise optimal means of combatting the growing burden of cancer.