We report the observation of multimode exciton-polaritons in single-crystalline microplates of a two-dimensional (2D) layered metal-organic framework (MOF), which can be synthesized through a facile solvothermal approach, thereby eliminating all fabrication complexities usually involved in the construction of polariton cavities. With a combination of experiments and theoretical modeling, we have found that the exciton-polaritons are formed at room temperature as a result of a strong coupling between Fabry-Perot cavity modes formed inherently by two parallel surfaces of a microplate and Frenkel excitons provided by the 2D layers of dye molecular linkers in the MOF. Flexibility in rational selection of dye linkers for synthesizing such MOFs renders a large-scale, low-cost production of solid-state, micro-exciton-polaritonic devices operating in the visible and near-infrared range. Our work introduces MOFs as a new class of potential materials to explore polariton-related quantum phenomena in a cost-effective manner. © 2019 American Chemical Society.