Modulating the catalytic activity of heterogeneous photocatalysts and simultaneously achieving selective and deep mineralization of refractory pollutants remains challenging. To solve this problem, we synthesized ZnO@FeNi-MOF/biomass waste-derived porous carbon (BC) nanoreactor and constructed a photocatalytic and peroxymonosulfate (PMS) activation synergistic tandem catalytic system. The core–shell structure of ZnO@FeNi-MOF leverages the size exclusion effects to enhance the selectivity towards micropollutants. Additionally, the constructed S-scheme heterogeneous interface serves as the reactive oxygen species generator. Highly porous and conductive BC serves as an excellent co-catalyst and a trap for pollutants. The nonradical pathway-dominated system further improves oxidative selectivity. We revealed typical antibiotics’ mineralization and detoxification pathways by experimental means and theoretical calculations. Furthermore, the long-term stable operation of the fixed bed continuous flow device shows high potential for engineering application. The research presents a viable approach for a tandem hybrid catalytic system that effectively and selectively eliminates organic contaminants.