In this article, we propose a space spreading-assisted framework that leverages either time or frequency diversity or both to reduce interference and signal loss owing to channel impairments and facilitate the efficient operation of large-scale dense Internet-of-Things (IoT). Our approach employs dispersion of data-streams transmitted from individual IoT devices over indexed space-time (ST), space-frequency (SF) or space-time-frequency (STF) blocks. As a result, no two devices transmit on the same block; only one is activated while the rest of the devices in the network is silent, thereby minimizing possibility of interference on the transmit side. On the receive side, multiple-antenna array ameliorates performance in presence of channel impairments while exploiting array-processing gain. As interference due to superposition of multiple data-streams is killed at its root, no extra energy is wasted in fighting interference and other impairments, thereby enabling energy-efficient transmission from multiple devices over multiple access channel (MAC). To validate the proposed concept, we simulate the performance of the framework against dense IoT networks deployed in generalized indoor and outdoor scenarios in terms of probability of signal outage. Results demonstrate that our conceptualized framework benefits from interference-free transmission as well as enhancement in overall system performance.