The rapid advancements in quantum computing necessitate a scientific and rigorous approach to the construction of a corresponding software ecosystem, a topic underexplored and primed for systematic investigation. This chapter takes an important step in this direction. It presents scientific considerations essential for building a quantum software ecosystem that makes quantum computing available for scientific and industrial problem-solving. Central to this discourse is the concept of hardware–software co-design, which fosters a bidirectional feedback loop from the application layer at the top of the software stack down to the hardware. This approach begins with compilers and low-level software that are specifically designed to align with the unique specifications and constraints of the quantum processor, proceeds with algorithms developed with a clear understanding of underlying hardware and computational model features, and extends to applications that effectively leverage the capabilities to achieve a quantum advantage. We analyze the ecosystem from two critical perspectives: the conceptual view, focusing on theoretical foundations, and the technical infrastructure, addressing practical implementations around real quantum devices necessary for a functional ecosystem. This approach ensures that the focus is toward promising applications with optimized algorithm–circuit synergy, while ensuring a user-friendly design, an effective data management, and an overall orchestration. This chapter thus offers a guide to the essential concepts and practical strategies necessary for developing a scientifically grounded quantum software ecosystem.