Cancer represents a profoundly complex, multiscale phenomenon involving cellular, tissue, and organismal levels of disruption. While traditional theories have focused on genetic and morphological abnormalities, growing evidence suggests that cancer is not merely a disease of uncontrolled cell growth but also a systemic disorder shaped by dynamic interactions between tumor cells and the host organism. Historical and contemporary theories—from aneuploidy and metabolic dysfunction to immune evasion and tissue disorganization—reflect the struggle to develop a unifying explanatory model. The seminal “hallmarks of cancer” framework offered by Hanahan and Weinberg provides a valuable scaffold, but recent work has expanded this to include systemic, ecological, and temporal dimensions. The tumor microenvironment, stromal coconspirators, and cancer-induced systemic rewiring—including neural, immune, and metabolic circuits—have emerged as critical determinants of cancer progression. With advances in multi-omics, AI-driven modeling, and systems biology, oncology is shifting toward integrative frameworks that consider cancer as a coevolving subsystem within the organism. This paradigm shift encompasses cancer’s bidirectional communication with its environment, cancer-stroma codependence, stress-response adaptations, and parasitic exploitation of organismal resources. Precision therapies must now move beyond targeting isolated genetic alterations or membrane antigens and include strategies that also modulate organismal homeostasis and systemic responses. Recognizing cancer as both a cellular phenomenon and a systemic state opens new therapeutic avenues, particularly in prevention and early intervention. A holistic approach integrating different biological scales may redefine cancer care and lead us from fragmented interventions toward sustainable, dynamic control of the disease.