Cancer does not evolve in isolation but rather within complex ecosystems that operate across spatial, temporal, and systemic scales. Within the tumor microenvironment, diverse cell populations assemble into specialized niches continually reshaped by systemic physiology, environmental inputs, and therapeutic pressure. Quail and Joyce propose a multi-scale framework that reframes therapeutic strategies from targeting maligant cells alone to reprogramming the cellular, vascular, and systemic networks that sustain disease, charting a path toward durable and curative precision oncology.