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In this paper, a cross-layer solution for packet size optimization in wireless sensor networks (WSN) is introduced such that the effects of multi-hop routing, the broadcast nature of the physical wireless channel, and the effects of error control techniques are captured. A key result of this paper is that contrary to the conventional wireless networks, in wireless sensor networks, longer packets reduce the collision probability. Consequently, an optimization solution is formalized by using three different objective functions, i.e., packet throughput, energy consumption, and resource utilization. Furthermore, the effects of end-to-end latency and reliability constraints are investigated that may be required by a particular application. As a result, a generic, cross-layer optimization framework is developed to determine the optimal packet size in WSN. This framework is further extended to determine the optimal packet size in underwater and underground sensor networks. From this framework, the optimal packet sizes under various network parameters are determined.