•Muscle-invasive bladder cancer (MIBC) has one of the highest mutation burdens across human cancers.•The Cancer Genome Atlas 2017 provided a comprehensive and integrated analysis of genomic, epigenetic, and transcriptomic alterations that has revolutionized our understanding and utilization of genomics in MIBC.•Integration of The Cancer Genome Atlas with other MIBC genomes may reveal unique genomic features of bladder cancer to guide prevention, diagnosis, prognosis, and ultimately cure. The Cancer Genome Atlas (TCGA) for bladder cancer was published in 2014 with updated annotation of over 400 patients with muscle-invasive bladder cancer (MIBC) in 2017. This tremendous work established the foundation of the genomic landscape of MIBC. The next steps to utilize information from The Cancer Genome Atlas is to (1) identify the causes of mutation, (2) determine the significant differences and sources of heterogeneity, and (3) apply these tools toward patient care. In this review, we discuss the full spectrum of the genomic landscape of MIBC toward the goal of therapeutic application.