The therapeutic potential of nucleic acids is expanding rapidly, but their rational design remains a significant challenge. We present XNA-Hub, an innovative software toolkit for the design, modification, simulation, and analysis of nucleic acids. It integrates a multi-step, substructure-based algorithm that combines molecular modeling with AI-based tools. With a growing library of chemical modifications and support for a wide variety of NA modalities, users can easily explore hundreds of therapeutic candidates. Its user-friendly graphical interface makes complex modeling accessible, accelerating rational drug design, reducing expensive trial-and-error approaches and facilitating the development of novel therapeutic nucleic acids.