Pamiparib and Temozolomide for the Treatment of Hereditary Leiomyomatosis and Renal Cell Cancer

Inclusion Criteria: * Subject has voluntarily agreed to participate by signing an informed consent * Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1 * Ability to swallow whole capsules * Histologically confirmed metastatic or unresectable renal cell carcinoma with morphologic features consistent with hereditary leiomyomatosis and renal cell cancer (HLRCC). This can include tumors with overlapping morphology previously called papillary, tubulocystic, tubulopapillary, collecting duct, or unclassified as long as in the HLRCC- spectrum * The presence of a documented germline fumarate hydratase (FH) alteration (mutation or deletion). This includes pathogenic or likely pathogenic alterations but may also include variants of unknown significance (VUS) in patients with strong personal or family history where the clinician makes a presumed clinical diagnosis * Progression on 1 or more lines of systemic therapies for metastatic disease. Neo/adjuvant therapy in the absence of documented distant disease does not count as a line of therapy * No known intolerance of study drugs or excipients, and able to comply with study requirements * Absolute neutrophil count (ANC) \>= 1,500 /microliter (mcL) (\< 2 weeks prior to day 1) * Platelets \>= 100,000 / mcL (\< 2 weeks prior to day 1) * Hemoglobin \>= 10 g/dL or \>= 6.2 mmol/L without transfusion or erythropoietin (EPO) dependency (within 2 weeks of first dose) * Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR m…