A fundamental challenge in strain engineering involves the rewiring of complex phenotypes. Conventional approaches for doing so fall short of expectations -- they rely upon recursive adaptation methods, which are slow, often result in dead-end or “sick” strains, and do not generate the basic understanding required for further engineering or intellectual property protection. Rather, quantitative and high-resolution methods capable of effectively exploring the breadth of functions present in a typical genome are required. We have previously reported the SCalar Analysis of Library Enrichments (SCALEs) method to not only monitor enrichment patterns across comprehensive genomic libraries but also to better understand the mechanisms directing selection for complex phenotypes. We have applied this approach to gain insights into the genetic and biochemical mechanisms underlying tolerance to a variety of chemicals, including 3-hydroxypropionic acid, acetate, succinate, ethanol, napthol, and various antimicrobials. While this approach has provided useful insights, it is limited in it's ability to simultaneously detect genes acting in-trans to alter a phenotype and does not detect disruptional mutational events. Thus, we initiated the development of a trackable, recursive, multiplex-recombineering (TReMR) approach that allows for simultaneous engineering multiple “up” or “down” mutations into a single strain as well as the highly parallel tracking of such mutations via a molecular barcoding strategy. We have demonstrated the complete construction and application of required genetic vectors and are currently applying this design at the genome scale. We will report upon the insights we have uncovered through the application of such tools for engineering complex phenotypes.