Recent research on the role of nanomaterials in gas hydrate science and a few review papers have highlighted the positive synergies between gas hydrates and metal–organic frameworks (MOFs) for gas separation and storage. Metal–organic frameworks consist of metal nodes and organic linkers connected by coordination bonds to form programmable modular structures that are symmetric and have tunable properties. Metal–organic frameworks, also known as microporous or nanoporous materials, provide a large pore volume and surface area suitable for capturing, separating and storing gases through physisorption mechanisms. However, water and water interactions within the nanopores, open metal sites, coordination bonds and surface make metal–organic framework usage in water-based technologies an exciting research topic. Water-based gas hydrate technology could be potential technology that can take advantage of MOF tunable properties, such as a large surface area and a high pore volume, to improve its efficiency and formation mechanism. For the authors of this review, the synergy of MOFs and gas hydrates resembles a Pandora’s box of unanswered questions and revelations. Therefore, this review examines the current state of the art, including present research on gas storage and separation using gas hydrates in the presence of a MOF. In addition, critical technical aspects, such as the water stability of MOFs, the nano confinement effect and water properties in the nanopores, are presented to stimulate critical thinking among scientists in hydrate research to fully exploit the synergies between MOFs and hydrates. This review ends with the authors’ opinion on potential research areas, unanswered questions and practical implications and prospects.