A simple and straightforward screening process to assess the toxicity and corresponding cell response of dental composites would be useful prior to extensive in vitro or in vivo characterization. To this end, gradient composite samples were prepared with variations in filler content/type and in degree of conversion (DC). The DC was determined using near infrared spectroscopy (NIR), and the surface morphology was evaluated by laser scanning confocal microscopy (LSCM). RAW 264.7 macrophage-like cells were cultured directly on the composite gradient samples, and cell viability, density, and area were measured at 24 h. All three measures of cell response varied as a function of material properties. For instance, compositions with higher filler content had no reduction in cell viability or cell density, even at low conversions of 52%, whereas significant decreases in viability and density were present when the filler content was 35% or below (by mass). The overall results demonstrate the complexity of the cell-material interactions, with properties including DC, filler type, filler mass ratio, and surface morphology influencing the cell response. The combinatorial approach described herein enables simultaneous screening of multiple compositions and material properties, providing a more thorough characterization of cell response for the improved selection of biocompatible composite formulations and processing conditions.