Background: Molecular tumor profiling (MTP) to guide therapy is increasingly being applied in the clinic, although how medical oncologists (MOs) manage this in clinical practice is not fully understood. Methods: An online survey explored MOs’ experience with MTP interpretation, treatment (tx) decisions, identifying resources, and communicating results to patients with cancer. MOs were identified based on their participation in the Australian Molecular Screening and Therapeutics Program. Results: 108 MOs (57% male, median years of practice, 5-9 years, 83% urban-based practice and median age range, 40-49 years) participated from June 2018 – Jan 2019. Most MOs had experience with MTP (90%), and felt it was their role to discuss results. MOs felt confident discussing the process of MTP, the probability of a ‘therapeutically actionable finding’, and results (score 70-75, range 0 least confident - 100 completely confident). However, almost two-thirds of MOs needed/wanted assistance with interpretation of results, favouring a Family Cancer Clinic (FCC) helpline, patient information sheets on MTP, and decision aids. In particular, MOs were less confident discussing germline results and their implications (median score 56) but were comfortable (median score 96) to refer to an FCC. Most MOs felt there was sufficient information on the MTP report to understand results. Some preferred to receive ‘all cancer gene variants’ (36%), others only those with clinical actionability (45%), and some only those with therapeutic actionability (19%). Most MOs (85%) wanted to know the full list of genes assayed, tx recommendations, and/or a list of relevant trials. Interestingly, MOs indicated little confidence that MTP would guide useful tx decisions (median score 51) and most reserved it for the tx-refractory setting. A minimal level of evidence supporting treatment was required by 83% of MOs prior to recommending biomarker-guided tx. Conclusions: MOs are increasingly integrating MTP into clinical practice, despite uncertainty about result validity and clinical translation, particularly regarding germline results. Understanding these potential barriers is the first step in developing clinician supports to facilitate clinical translation.