The last few decades have witnessed the unprecedented explosion of a new research field built around Metal-Organic Frameworks (MOFs). MOFs are crystalline porous solids consisting of metal ions (also named clusters) coordinated to often rigid organic molecules (also called ligands) to form one- two-, or three- dimensional structures. This combination of organic and inorganic building blocks into highly ordered, crystalline structures offers an almost infinite number of combinations, enormous flexibility in pore size, shape and structure, and plenty of opportunities for facile tuning by functionalization, grafting and/or encapsulation. This field has rapidly evolved from an early stage, in which the main scope was the discovery of new structures, to a more mature stage in which dozens of applications are currently being explored like gas storage, separation, sensing or drug delivery. Last but not least, its tunable morphology, pore size, and adsorption properties, along with its intrinsic hybrid nature, all point at MOFs as very promising heterogeneous catalyst. This dissertation describes the development of a new generation of hybrid catalysts based on Metal-Organic Frameworks decorated with active functionalities and the study of its implementation into challenging catalytic processes. Metal clusters with unsaturated sites, organic functionalities and encapsulation of macromolecules or nanoparticles in the pores of these tunable crystalline structures are among the methods investigated in this dissertation. This work investigates from the design of the catalysts to the final application: from the molecular to the reactor scale. The research presents a deep insight in successful methodologies for future multifunctional systems and the catalytic performance of such active sites when confined into highly ordered structures, supported by extensive characterization.