Applying magnetic nanostructures in high density magnetic data storage is hindered by a lack of suitable substrate. Using density functional theory, we explored the potentiality of graphyne as a template for nanomagnetic bits. Due to the unique porous structure of graphyne, Os atom tightly binds to the graphyne at the hollow site with an in-plane MAE of 18 meV. Through a rigid band model, we introduced the strategy to manipulate the MAE by rearrangement of d-orbitals of Os atom. A large MAE of about 48 meV was obtained for F functionalized Os@graphyne. To obtain the out-of-plane easy axis, we have considered the MAE of several transition-metal combinations. We finally identified Os–Os@graphyne as an excellent candidate for room temperature applications due to the high MAE and the structural stability.