Dense user node deployments are soon to become a common theme with the Machine to Machine (M2M) communication networks steadily gaining momentum. One of the major network design scenarios in the Internet of Things (IoT) is an efficient information gathering uplink. Furthermore, the uplink is of major interest owing to the significant design and protocol challenges that are present in a centralized or self-organizing contention based system. Therefore, in this thesis, we have presented a number of interference-aware innovative solutions based on a multiple sub-band uplink where frequency resource is allocated dynamically to optimize key performance criteria. We have shown in this thesis that choosing appropriate interference-aware sub-band allocation strategies, we can significantly improve the channel efficiency and energy efficiency of these M2M uplink systems. In particular, for an Access Point (AP) controlled uplink systems in Wireless Local Area Network (WLAN), we first present a novel multi-band system with significantly reduced contention using node position aware sectored clustering to dynamically allocate frequency sub-bands. In dense user M2M networks spread over a large geographical distance, nodes from overlapping Basic Service Set (BSS) cause a large amount for cross BSS interference. Therefore, we present novel interference measure based on detailed analysis of node neighborhood including channel quality, uplink traffic requirements, user node density etc. The Interference-Aware Dynamic Frequency sub-band Allocation scheme (IDFA) scheme using on the above interference measure can achieve significantly higher uplink throughput and up to 2-3 times better channel efficiency compared to existing IEEE 802.11ah uplink. Improved channel efficiency in IDFA contributes to about 30% improvement in energy consumption at the nodes. An important contribution of this thesis is to study and implement a communication system using a neighborhood interference-aware multi-hop transmission scheme in a scalable uplink Orthogonal Frequency Division Multiple Access (OFDMA) system targeting health monitoring M2M application. Transmit beamforming/receiver combining is also employed to reduce neighborhood interference and further improve the energy efficiency of the uplink. This implementation shows the importance of flexibility of design parameters in OFDMA for M2M applications with varying traffic requirements and energy budgets. Finally, the design of the OFDMA uplink transceiver based on IEEE 802.11ah and the Over the Air (OTA) transmission experiments, show the feasibility and illustrate the real-implementation design challenges in a multi-band uplink.