We presented a case with left sided UC previously managed effectively with mesalamine with deep remission, who was diagnosed with lung adenocarcinoma. She received pembrolizumab for five cycles which worsened her UC, despite mesalamine maintenance. Pemetrexed and carboplatin were added to pembrolizumab, which led to progressive worsening of her UC. The UC disease course was refractory to oral budesonide, had a transient response to vedolizumab induction x 2 doses that worsened with chemo resumption, a transient response to infliximab induction x 3 doses, but then relapsed after chemo resumption again, which was refractory to a booster dose of infliximab 10mg/kg. Given her severe ongoing symptoms, she was started on upadacitinib while holding chemotherapy which led to clinical and biochemical remission with normalization of fecal calprotectin and remained on maintenance of upadacitinib. Her colitis remained in remission clinically, endoscopically and biochemically over 5+ months of treatment with pemetrexed plus upadacitinib. Her cancer has had a durable response over 12 months of follow-up, with the most recent scan showing possible low volume progression of disease that may require further adjustment on her cancer regimen.