AbstractDevelopment of the powerful building block is of great significance to construct materials with advanced properties. Herein, for the first time, a triazole‐based luminescent core with balanced twist and conjugation is reported, which is explored to construct a D‐A near‐infrared (NIR) aggregation‐induced emission luminogens (TPT‐DCM) with high molar extinction coefficient, good brightness and excellent reactive oxygen species generation rate. These features enable it to function as a nanoprobe with ultralong NIR afterglow luminescence (up to 20 days) and ultrahigh tumor‐to‐liver signal ratio (up to 187) for in vivo deep‐tissue afterglow imaging (with depth reaching 1.6 cm), in combination with chemiluminescence resonance energy transfer aided by active Schaap's dioxetane. Moreover, thanks to the excellent properties of the nanoprobe, the afterglow imaging‐guided surgery navigation can be successfully conduced to remove the tumors especially with tiny size of < 1 mm. This is particularly useful to eliminate tumor residuals and prevent the cancer recurrence after surgery.