AbstractDeveloping metal–organic frameworks (MOFs) with strong near‐infrared II (NIR‐II, 1000–1700 nm) emission is significant for biomedical research but highly challenging. So far there are no MOFs reported for NIR‐II imaging in vivo due to their poor NIR‐II emission efficiency. Herein, a strategy is proposed to prepare MOFs with strong NIR‐II emission, by integrating NIR dye IR‐3C and Ln3+ (Ln = Yb, Nd, and Er) into a same framework. IR‐3C with high photon‐absorption ability harvests the excitation photons and transfers energy to Ln3+ via a resonance energy transfer pathway, significantly enhancing the NIR‐II emission of Ln3+. The as‐obtained Er‐BTC‐IR exhibits excellent NIR‐IIb (1500–1700 nm) emission efficiency in aqueous phase and good biocompatibility after surface modification, which provides advanced bioimaging performance in vivo. It is able to clearly delineate the vessels, spine, and lymph of mice, and also to differentiate the vessels with acute vascular inflammation. This strategy paves the way to the preparation of NIR‐II emissive MOFs and will promote their bioapplication.