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Despite advancements in capacity-enhancing technologies like massive MIMO (multiple input, multiple output) and intelligent reflective surfaces, network densification remains crucial for significant capacity gains in future networks such as 6G. However, network densification increases interference and power consumption. Traditional cellular architectures struggle to minimize these without compromising service quality or capacity, which necessitates a shift to a user-centric radio access network (UC-RAN). The UC-RAN approach offers additional degrees of freedom to ease the spectral-energy efficiency interlock while improving the service quality. However, its increased degrees of freedom make its optimal design and operation more challenging. This dissertation introduces four novel approaches for UC-RAN optimal design and operation. The objectives include mitigating interference, reducing power consumption, ensuring diverse user/vertical service quality, facilitating proactive network operation, risk-aware optimization, adopting an open radio access network, and enabling universal coverage. First, we construct an analytical framework to assess the effects of incorporating Coordinated Multipoint (CoMP) technology into UC-RAN to reduce interference and power consumption. We use stochastic geometry tools to derive expressions for network-wide coverage, spectral efficiency, and energy efficiency as a function of UC-RAN Configuration and Optimization Parameters (COPs), including data base station densities and user-centric service zone sizes. While the analytical framework provides insightful performance analysis that can guide …