This chapter highlights the potential of engineering Escherichia coli for the development of powerful therapies against cancer. It reviews the status of bacterial therapies against cancer and the application of commensal and probiotic E. coli strains as vectors for tumor colonization and delivery of therapeutic proteins. The chapter discusses the use of synthetic biology for a complete design of E. coli bacteria for tumor therapy, incorporating modular elements and gene circuits responding to tumors. It describes the development of modular elements for the specific adhesion of E. coli bacteria to tumors and for the injection therapeutic proteins into the tumor cells. The chapter explores the expression of synthetic adhesins could favor tumor colonization at low bacterial doses. The field of synthetic biology is emerging to bring engineering approaches into biomedicine. Using tools from synthetic biology, researchers have the capability to engineer gene circuits that allow bacteria to communicate and express therapeutic or diagnostic molecules inside tumors.