Systems and methods described herein align various types of hypervisor threads with a non-uniform memory access (NUMA) client of a virtual machine (VM) that is driving I/O transactions from an application so that no remote memory access is required and the I/O transactions can be completed with local accesses to CPUs, caches, and the I/O devices of a same NUMA node of a hardware NUMA system. First, hypervisor of the VM detects whether the VM runs on a single or multiple NUMA nodes. If the VM runs on multiple NUMA nodes, a NUMA client on which the application is executing the I/O transactions is identified and knowledge of resource sharing between the NUMA client and its related hypervisor threads is established. Such knowledge is then utilized to schedule the NUMA client and its related hypervisor threads to the same NUMA node of the NUMA system.