Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesics and antipyretics, which form an interesting drug group because of their new and alternate functions. The ability of the NSAIDs belonging to the oxicam chemical group to induce membrane fusion at low physiologically relevant concentrations is a new function that has drawn considerable attention. Membrane fusion is dependent on the interplay of physicochemical properties of both drugs and membranes. Here, we have elucidated the effects of different oxicam drugs, Meloxicam, Piroxicam, Tenoxicam, Lornoxicam, and Isoxicam, on an identical membrane-mimetic system. This highlights only the differential effects of the drugs on drug membrane interactions, which in turn modulate their role as membrane fusogens. The partitioning behavior and the location of the drugs in dimyristoylphosphatidylcholine vesicles have been studied using second-derivative absorption spectroscopy, fluorescence quenching, steady-state fluorescence anisotropy, and time-resolved fluorescence lifetime measurements. Fusion kinetics has been monitored by fluorescence assays and dynamic light scattering was used to provide a snapshot of the vesicle diameter distribution at different time points. The differential perturbing effect of the drugs on the membrane is dependent both on their partitioning and location. Although partitioning governs the extent of fusion, the location modulates the rates of each step.