AbstractThe development of highly efficient catalysts to address the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) in lithium‐sulfur batteries (LSBs) remains a formidable challenge. In this study, a series of multi‐site catalytic metal‐organic frameworks (MSC‐MOFs) were elaborated through multimodal molecular engineering to regulate both the reactant diffusion and catalysis processes. MSC‐MOFs were crafted with nanocages featuring collaborative specific adsorption/catalytic interfaces formed by exposed mixed‐valence metal sites and surrounding adsorption sites. This design facilitates internal preconcentration, a coadsorption mechanism, and continuous efficient catalytic conversion toward polysulfides concurrently. Leveraging these attributes, LSBs with an MSC‐MOF‐Ti catalytic interlayer demonstrated a 62 % improvement in discharge capacity and cycling stability. This resulted in achieving a high areal capacity (11.57 mAh cm⁻²) at a high sulfur loading (9.32 mg cm⁻²) under lean electrolyte conditions, along with a pouch cell exhibiting an ultra‐high gravimetric energy density of 350.8 Wh kg⁻¹. Lastly, this work introduces a universal strategy for the development of a new class of efficient catalytic MOFs, promoting SRR and suppressing the shuttle effect at the molecular level. The findings shed light on the design of advanced porous catalytic materials for application in high‐energy LSBs.