The translation of biomarker sensing into programmable diagnostics or therapeutic applications in vivo is greatly challenging, especially for eliminating the 'false positive' signals from OR logic gates. Herein we present a sense-of-logic dual-channel nanoprobe, operating through a sequence-activated AND logic gate by responding ultra-sensitively to pH changes and being subsequently triggered with biothiol for the controllable release of anti-cancer drugs. Specifically, programmable drug release is conducted in a multistage tumor microenvironment (acidic endocytic organelles followed by abnormal glutathione-overexpressing cell cytosol), which is synchronous with dual-channel near-infrared (NIR) fluorescence output. This approach represents the merging of sensing and release, including logically enabled molecular design, biomarker sensing, and controllable drug release. Impressively, the sequential AND logic feature within an unprecedented framework provides feedback on the diversity and complexity of biological milieu, along with remarkably enhancing the tumor therapeutic efficiency via its precise targeting ability and programmable drug release.