Human cytomegalovirus (HCMV) is known to cause severe sequalae in both immature and immunosuppressed populations. While much is known about its pathology, our understanding of many viral processes is limited. Bioinformatic and traditional virology methods were utilized to further evaluate the virus:host relationship, specifically the events leading to the envelopment and egress of HCMV. We analyzed two previously generated datasets characterizing the transcriptional and proteomic profiles of HCMV infected human foreskin fibroblasts. These analyses were supplemented by gene ontology to generate a novel model detailing the pathways potentially utilized during the egress of nascent virions. Separately we provide new insights into the function of HCMV tegument protein pUL103 utilizing two proteomics approaches, and thereby identified 13 viral and 18 cellular potential interaction partners. These analyses serve to highlight the utility and flexibility of systems biology approaches to virology, as well as provide novel insights into HCMV pathogenesis.