Combination cancer therapy possesses considerable appeal due to its many merits such as enhancing efficacy by synergistic effects and overcoming drug resistance as compared to monotherapy. Nanomedicine-mediated co-delivery of multiple anticancer agents is more effective than conventional cocktail-based physical mixture of free drugs. A strategy is required to differentiate their unique targets for maximizing the synergistic effects based on individual sites of action of different drugs. This review summarizes the recent progresses in nanomedicine-based combination cancer therapies using site-specific co-delivery strategies, which have been classified by different target sites at the anatomical scales such as tissue, cellular and subcellular levels. In particular, the design of materials and formulations functionalized with tumor-associated signal-responsive elements has been highlighted. The potential and perspective of future developments have also been discussed.