Removal of 99TcO4− from the nuclear fuel cycle remains a great challenge due to the harsh environment such as strong acid/alkali. Here, a methyl-rich cationic polymer network (TBT-TCB) was obtained by molecular engineering and used for 99TcO4− removal in extreme environments. The bulk methyl groups in the vicinity of imidazole units greatly enhance the base-resistance of TBT-TCB owing to the steric hindrance and electronic effects, which avoid OH− induced imidazole ring-opening reactions, resulting in a ReO4− (a surrogate of 99TcO4−) removal efficiency of 85% under 1 M NaOH. Meanwhile, the introduction of methyl groups into TBT-TCB enhances its hydrophobicity, resulting in improved affinity for the larger and less hydrophilic 99TcO4−. Consequently, TBT-TCB exhibits high removal efficiency even in the presence of strong competing ions, achieving a remarkable 84% removal rate in 1 M H2SO4. More importantly, TBT-TCB shows excellent robustness and reusability (>5 cycles), high absorption selectivity, and rapid adsorption kinetics for 99TcO4−/ReO4−. Furthermore, chromatographic column experiments with TBT-TCB have shown their great potential for industrial applications.