Genomic Sequencing in Determining Treatment in Patients With Metastatic Cancer or Cancer That Cannot Be Removed by Surgery

Inclusion Criteria: * Patients with unresectable cancer for which there are genomic drivers with corresponding Food and Drug Administration (FDA) approved or experimental drugs available, e.g. non-small cell lung cancer; and/or patients with histologically confirmed metastatic malignancy that have failed standard treatment or cannot tolerate standard treatment as deemed by the treating physician * Malignancy must be measureable as per appropriate guidelines * Patients who are willing to provide a specimen for genomic sequencing * Preferred method: * Tumor cell sample available and of sufficient quantity in the Tumor Tissue Shared Resource or patients who are willing to undergo additional tissue collection for tumor genomic sequencing through FoundationOne; available specimens must have been harvested within two years to be eligible * Alternative method: * Patients who are unwilling or unable to provide a tumor tissue sample and who undergoes Guardant360 sequencing may be considered eligible by the treating physician * Patients who have already had their specimens sent for genomic sequencing are eligible provided they have not received their sequencing results at the time of enrollment * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Absence of clinically relevant liver or kidney failure as deemed by the treating physician * Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document Exclusion Criteria: * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diminished mental capacity or psychiatric illness/social situations that would limit compliance with study requirements * Pregnancy or lactation