NB-IoT is a promising cellular technology for enabling low cost, low power, long-range connectivity to IoT devices. With the bandwidth requirement of 180 kHz, it provides the flexibility to deploy within the existing LTE band. However, this raises serious concerns about the performance of the technology due to severe interference from multi-tier 5G HetNets. Furthermore, as NB-IoT is based on HD-FDD, the symmetric allocation of spectrum band between the downlink and uplink results in underutilization of resources, particularly in the case of asymmetric traffic distribution. Therefore, an innovative RRM strategy needs to be devised to improve spectrum efficiency and device connectivity. This article presents the detailed design challenges that need to be addressed for the RRM of NB-IoT and proposes a novel framework to devise an efficient resource allocation scheme by exploiting cooperative interference prediction and flexible duplexing techniques.