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.