The 2010-2015 period saw a decisive shift toward three-dimensional, microphysiological cancer models that replicate tumor architecture, stiffness, and cell–matrix interactions. Researchers integrated microfluidic platforms to generate perfusable, endothelialized vascular networks on a chip, enabling realistic tumor vasculature studies and accurate modeling of drug-transport dynamics. Concurrently, multistage nanoparticle delivery systems emerged to navigate complex tumor microenvironments, while three-dimensional biomaterials catalyzed a broader move away from two-dimensional culture toward more faithful tumor recreations. Breakthroughs in programmable carriers, including DNA origami strategies, and biomimetic exosome-like vesicles, expanded options for targeted, stable chemotherapeutic delivery in vivo. Historical Significance: This era consolidated the shift from traditional two-dimensional culture to three-dimensional, integrative cancer engineering platforms, bridging materials science, nanomedicine, and tumor biology. The groundwork was laid for organ-on-chip cancer research, vascularized tumor modeling, and advanced biomimetic and programmable nanocarrier approaches—foundations that shaped subsequent strategies in precision therapy and engineered cancer ecosystems.