The ability to finely tune Poisson’s ratios is pivotal in customizing the mechanical behavior of 3D metamaterials. The inverse design of these materials empowers designers to optimize their Poisson’s ratios according to specific requirements, thereby enhancing their adaptability and versatility across a broad spectrum of applications ranging from soft robots to wearable technologies. This study proposes an innovative and accessible inverse design framework to conceptualize 3D metamaterials through a set of geometric parameters for crafting to ensure programmability, tailored Poisson’s ratios, and resilience to large deformations. Several innovative classes of 3D metamaterials with unique tailorable Poisson’s ratios under substantial deformations are presented, marking a significant paradigm shift in material design. The Poisson’s ratios of a selected sequence of metamaterials are validated through comprehensive numerical simulations and quasi-static tensile tests. Overall, this study delivers effective guidelines to design 3D metamaterials with customizable and programmable Poisson’s ratios over large deformations.