Comprehensive Summary To gain insights into the potential of thianthrene (TA), its substituent effects were systematically studied on the room‐temperature phosphorescence (RTP) properties, including the electron‐donating and electron‐withdrawing substituents at 1‐ and 2‐positions of TA, respectively. Both theoretical and experimental investigations show that the 2‐position electron‐withdrawing substituents greatly enhance RTP performance than the 1‐position substituents, while the situation is exactly the opposite for electron‐donating substituents. Compared with the 1‐position substitution, the 2‐position electron‐withdrawing substituents induce the higher RTP radiation rate and lower non‐radiation rate, in favor of the enhancement of RTP efficiency. Furthermore, the introduction of phenylene into the 2‐position substitution greatly suppresses the non‐radiation, resulting in the simultaneously improved RTP efficiency and elongated lifetime. Finally, using these RTP materials, the dynamically reversible operations of information (write‐read‐erase) are realized, as well as the encryption and time‐dependent decryption demonstration. This work not only provides a better understanding of structure–property relationship on TA‐based RTP materials, but also suggests an intramolecular structural modification strategy to improve the performance of pure organic RTP materials.