Background: Academic Medical Centers (AMC) and community practices are implementing Molecular Tumor Boards (MTB) to interpret next-generation sequencing (NGS) results and develop clinical guidelines for utilizing NGS results. Reports of MTB experiences from cancer centers nationally vary in their abilities to translate molecular test results to actionable recommendations for their patients. In these efforts, there is not yet a definition for parameters of patients who would benefit most from a Precision Oncology approach. Methods: Defining Platforms for Individualized Cancer Treatment (DePICT) is an IRB approved registry trial designed to monitor outcomes of Broward County, FL residents with late-stage refractory cancer (ECOG ≤2) who undergo NGS. After consent, the MTB used NGS results to match patients to targeted clinical trials and therapies. The patients are followed at 12 week intervals. DePICT has consented 141 patients, out of which 111 have had at least one follow up. We analyzed these cases to identify key characteristics of patients that benefit most from NGS testing and MTB review. Groups were defined as those who pursued targeted therapies versus those who pursued standard of care or palliative regimens. Kaplan Meier survival analyses were done in R 3.4.3. Results: Patients with ≤3 previous lines of therapy were more likely to pursue targeted therapy than patients with ≥4 lines of therapy (32% vs. 17%, p = 0.045). Only patients with an ECOG score 0 or 1 pursued targeted therapy. An analysis of this population (ECOG < 2, ≤3 lines of therapy) revealed that patients on targeted therapy performed better than their palliative care counterparts. Median overall survival (mOS) for patients who received targeted therapy is 84 weeks (95% CI 36-Not Reached (NR)) and the mOS for patients who did not undergo targeted therapies was 36 weeks (95% CI 36-NR). Conclusions: This analysis identifies patients who may benefit most from NGS testing. Patients with ECOG scores of 0 or 1 and 3 or fewer lines of therapy were more likely to go on targeted therapy, and have better outcomes. Patients should be evaluated by precision oncology approaches earlier in their cancer care continuum.