Multiple immune components in the complex and heterogeneous tumor-immune microenvironment (TIME) work cooperatively to promote or impede cancer immunotherapy. Synergistically co-managing multiple immune cells with single agents for advanced antitumor immunity remains desirable but challenging. This In Focus article introduces a triple orthogonal linker (T-Linker)-based multimodal targeting chimera (Multi-TAC) platform, enabling the single-agent-mediated tumor-targeted co-engagement of multiple immune cell types within TIME for potentiated immunotherapy.