This study proposes a novel methodology, mixture-amount modeling (MAM), to investigate cross-media advertising synergy based on consumers’ media usage. MAM allows to derive optimal media mixes that can be different for different types of media users. The authors provide a proof of concept by analyzing 46,852 responses to 92 beauty care advertising campaigns from 10,972 respondents from the Netherlands, Belgium, Finland, and Hungary and demonstrating the impact of consumers’ combined magazine, television, and Internet usage (i.e., how intensively they use media overall and the relative proportion of each individual medium) on their campaign-evoked brand interest, perceived brand equity, and purchase intention for advertised brands. The results suggest that different patterns of consumer media usage result in different responses to advertising campaigns.