Gold nanocages (AuNCs) with hollow interiors, porous walls, and tunable localized surface plasmon resonance (LSPR) peaks in the NIR region represent a promising platform for therapeutic applications, and can be used for orthogonally triggered release by choosing the right laser according to the AuNC's LSPR. AuNCs are prepared with different LSPRs and covered with a smart polymer shell. Laser irradiation in resonance with the LSPR can trigger the release of a pre-loaded effector. As a proof of concept, enzyme and substrate (prodrug) are selectively released from two different AuNCs. Enzymatic reactions only occur after successful opening of both types of AuNC capsules. The system acts as an “AND” logic gate. Furthermore, if the AuNC is loaded with isoenzyme or enzyme inhibitor, an “OR” or “INHIBIT” logic gate operation is achieved. To the best of our knowledge, no reports have combined NIR light-encoded orthogonally triggered release with “prodrug” activation processes to realize defined different logic operations for regulating the dosage of active drug in a specific region. The design is simple and spatial/temporal to control, and provides new insights into developing NIR light-encoded, logically controlled, intracellular release systems.