Cyclospora cayetanensis remains a poorly controlled foodborne pathogen despite decades of research and major advances in molecular detection and genomic characterization. This review critically re-evaluates three foundational assumptions that continue to shape research, diagnostics, and public health practice. First, the widespread use of Eimeria and Cryptosporidium as surrogate organisms is examined in light of the limited direct validation of their ability to reproduce key biological characteristics of C. cayetanensis, particularly with respect to sporulation, environmental persistence, and intervention efficacy. Second, emerging phylogenetic and genomic evidence indicates that human-infecting Cyclospora comprises multiple genetically distinct lineages with reproductive isolation, raising important questions regarding taxonomy, epidemiology, transmission, and virulence. Third, the host-parasite-immune axis remains incompletely understood, particularly the mechanisms underlying the greater severity, persistence, and recurrence of infection in immunocompromised individuals. Across these three areas, the evidence reveals a persistent gap between what can be detected and what can be effectively prevented or controlled. The review therefore proposes a translational research framework that links foundational biological investigation to intervention development, implementation, and public health practice. Key priorities include direct validation of surrogate models, improved genomic resolution, standardized methods for assessing oocyst viability and infectivity, stronger agricultural water and on-farm controls, real-time molecular surveillance and traceback, and improved therapeutic and preventive strategies for vulnerable populations. Progress in controlling cyclosporiasis will require a shift from predominantly descriptive research toward evidence-based, actionable approaches that translate biological and technological advances into measurable reductions in transmission and disease.