The heterogeneous network (HetNet) architecture unprecedentedly reusing spectrum faces a critical challenge of interference mitigation among cells. For this goal, existing solutions successfully reaching resource orthogonality, however, impose critical assumptions of ubiquitous synchronization among all cells. Lacking of an effective network synchronization scheme, the installation of existing solutions is obstructed. This challenge motivates us to comprehensively study all-embracing solutions including two categories: synchronous and asynchronous based resource orthogonality schemes. In the first category, to be compatible with existing synchronous resource orthogonality techniques, we propose a series of timing alignment schemes by innovations of gossip algorithm and voter algorithm. In the second category, we avoid the synchronous framework to propose an asynchronous resource management inspired from game theory. The equally outstanding performance in both categories reveals an engineering duality on timing alignment and resource orthogonality, to provide foundations and design paradigm shifts toward the fifth generation (5G) HetNet.