This work presents innovative origami optimization methods for the design of unit cells for complex origami tessellations that can be utilized for the design of deployable structures. The design method used to create origami tiles utilizes the principles of discrete topology optimization for ground structures applied to origami crease patterns. The initial design space shows all possible creases and is given the desired input and output forces. Taking into account foldability constraints derived from Maekawa’s and Kawasaki’s theorems, the algorithm designates creases as active or passive. Geometric constraints are defined from the target 3D object. The periodic reproduction of this unit cell allows us to create tessellations that are used in the creation of deployable shelters. Design requirements for structurally sound tessellations are discussed and used to evaluate the effectiveness of our results. Future work includes the applications of unit cells and tessellation design for origami inspired mechanisms. Special focus will be given to self-deployable structures, including shelters for natural disasters.