Symbiosis between microbial associates and a host is a ubiquitous feature of life on earth, modulating host phenotypes. In addition to endosymbionts, organisms harbour a collection of host-associated microbes, the microbiome that can impact important host traits. In this opinion article we argue that the mutual influences of the microbiome and endosymbionts, as well as their combined influence on the host, are still understudied. Focusing on the endosymbiont Wolbachia, we present growing evidence indicating that host phenotypic effects are exerted in interaction with the remainder microbiome and the host. We thus advocate that only through an integrated approach that considers multiple interacting partners and environmental influences will we be able to gain a better understanding of host-microbe associations.