ABSTRACT Over recent epoch, initial uplink synchronization has become an essential part of the wireless communication systems owing to its amenities in the identification of new users to originate communication. Yet, allocating and sharing resources to users is a bottleneck due to the interference caused by multiple users. Besides, preceding works didn't concentrate on the usage of an effective mechanism to estimate the parameters of the received signal in the multiuser synchronization environment. These downsides affect the throughput and spectrum efficiency of the designed OFDMA system. To address these bottlenecks, this paper proposes the Joint Initial Uplink Synchronization and Interference Aware Resource Allocation (JIUS-IRA) in the Multi-User OFDMA system. JIUS-IRA comprises four processes: Parameter Estimation, Optimum Antenna Selection, Resource Allocation, and Resource Sharing. Initially, JIUS-IRA executes the Fast Block Least Mean Square-based Parameters Estimation Scheme (FBLMS-PES) to estimate the user parameters. To reduce the power consumption during transmission between 5G MIMO base station and users, JIUS-IRA selects the optimal antenna for transmission. The Sign Rank Oriented Resource Allocation (SO-RA) method is executed to allocate sub-channel resources to the cellular user. The resource requirement of D2D users present in the OFDMA system is resolved via the Harris Hawks Optimizer based Resource Sharing Scheme (H2ORSS). The numerical results acquired from the simulation are highly confidential with regard to metrics Root Mean Square Error (RMSE) of timing estimation (∼0.006), RMSE of power estimation (∼0.0079), RMSE of frequency estimation (∼ 0.008), Throughput (∼95%), Spectrum Efficiency (∼11.9 bps), and Complexity (0.045 × 104).