Palladium nanoparticles have been immobilized into an amino‐functionalized metal–organic framework (MOF), MIL‐101Cr‐NH2, to form Pd@MIL‐101Cr‐NH2. Four materials with different loadings of palladium have been prepared (denoted as 4‐, 8‐, 12‐, and 16 wt %Pd@MIL‐101Cr‐NH2). The effects of catalyst loading and the size and distribution of the Pd nanoparticles on the catalytic performance have been studied. The catalysts were characterized by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier‐transform infrared (FTIR) spectroscopy, powder X‐ray diffraction (PXRD), N2‐sorption isotherms, elemental analysis, and thermogravimetric analysis (TGA). To better characterize the palladium nanoparticles and their distribution in MIL‐101Cr‐NH2, electron tomography was employed to reconstruct the 3D volume of 8 wt %Pd@MIL‐101Cr‐NH2 particles. The pair distribution functions (PDFs) of the samples were extracted from total scattering experiments using high‐energy X‐rays (60 keV). The catalytic activity of the four MOF materials with different loadings of palladium nanoparticles was studied in the Suzuki–Miyaura cross‐coupling reaction. The best catalytic performance was obtained with the MOF that contained 8 wt % palladium nanoparticles. The metallic palladium nanoparticles were homogeneously distributed, with an average size of 2.6 nm. Excellent yields were obtained for a wide scope of substrates under remarkably mild conditions (water, aerobic conditions, room temperature, catalyst loading as low as 0.15 mol %). The material can be recycled at least 10 times without alteration of its catalytic properties. And the winner is…︁The catalytic activity of Pd nanoparticles immobilized on MIL‐101‐NH2 was studied as a function of the amount of Pd loaded into the metal–organic framework. For the first time, the importance of fine‐tuning this parameter is presented. This study has resulted in an excellent heterogeneous catalyst for Suzuki–Miyaura cross‐coupling reactions in water at room temperature.