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Powder densification for specified shaped metal–organic frameworks (MOFs) is desirable for most applications. The obtainment of such properties is challenging, one of which is the rapid crystal-to-amorphous transition (framework collapse) of MOFs under pressure. Herein, we found that the residual guests of the MOF-5 synthesis process could form binding groups based on the hydrogen-bonding networks of water. The improved processability and ease of compression, which did not promote rapid structure collapse, can be achieved in the guest-loaded MOF-5. Correspondingly, enhanced volumetric specific surface area and methane uptake of MOF-5 were obtained. This work focuses on a commonly neglected but positive function of the residual guests in MOFs, besides supporting the framework. MOFs loaded with multiple types of guests show attractive mechanical properties via guest–guest and guest–host interactions for powder densification, highlighting their commercial applications.