Non-orthogonal multiple access (NOMA) schemes allow multiple users to share the same resource and separate the users in either the power-domain (PD -NOMA) or in the code domain (CD-NOMA). To make NOMA a reality in networks, several important practical challenges need to be considered. This thesis addresses some of these challenges in both the PD-NOMA and CD-NOMA space. In PD-NOMA systems integrated with mmWave technology, the thesis considers the practical constraint of the end user processing capabilities, modelled through an successive interference cancellation (SIC) decoding capability constraint that captures the number of other user's signals any given user can decode in the SIC decoding procedure. 6G networks are expected to include a mix of users of varying processing capabilities, all needing to access the same spectrum. To solve the rate maximization problem when each user has different processing capabilities, the thesis proposes low-complexity heuristics to maximize the sum-rate after factoring in each individual users SIC decoding capability constraint. However, these algorithms are based on the instantaneous channel conditions of users and need to be run on a millisecond granularity. To address this, a machine learning based neural network approach is proposed that takes this complexity offline where the neural network is trained on simulated and past network data, and the trained network is directly applied to solve the clustering problem in live networks. The thesis also addresses the practical constraint around the availability of CSI by exploiting the growing field of integrated communication and sensing solutions using a camera equipped base station to aid the user clustering process in NOMA. In CD-NOMA systems using the widely promoted sparse code multiple access (SCMA) scheme for uplink (UL) NOMA, the thesis studies the PAPR problem in UL SCMA-OFDM systems. A novel link between the obtained PAPR statistics and the SCMA modulation scheme and the placement of the sub-carriers (SC's) that carry the SCMA codewords is presented. The thesis highlights unique opportunities that SCMA-OFDM systems present to the widely studied PAPR problem due to the I would like to express sincere gratitude to my supervisor, Prof. Halim Yanikomeroglu, for (a) believing in me and giving me the opportunity to pursue this Ph.D. degree while studying part-time, and (b) motivating me and providing continuous support throughout my Ph.D. study and research. I would like to acknowledge the people I got to collaborate with at different points in this journey. Particularly, I want to thank Monirosharieh Vameghestahbanati who provided me guidance during my early days and also Omar Maraqa, with whom I got to collaborate extensively on a number of different papers during my Ph.D. I would also like to acknowledge Ericsson Canada, to whom I was employed throughout this degree, for providing tuition assistance and encouragement throughout the years.I am deeply grateful to my parents for all their support and encouragement over many y...