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Background In early 2020, the COVID-19 pandemic created difficulties in clinical and organizational fields. Healthcare workers needed to protect their health and avoid infecting their family members, but also limit the virus’s spread among vulnerable oncology patients undergoing hospital treatment. Objective To evaluate the resilience and coping strategies of nurses working in the oncology setting. Methods A mixed-methods study was conducted. First, two questionnaires (CD-RISK and COPE- NVI-25) were used to assess nurses’ resilience strategies and coping mechanisms quantitatively. Second, qualitative semi-structured interviews were conducted to explore the personal experiences of nurses who cared for patients during the pandemic, and Colaizzi’s framework was used for content analysis. Results The 164 participants, the majority of whom were female (88.4%), reported high resilience. The CD-RISK score varied according to education. With respect to COPE-NIV-25, transcendent orientation and avoidance strategies had the lowest mean scores, while problem orientation was higher in nurses aged ≥ 40. Five themes emerged: (1) changes in work and personal areas; (2) feelings/emotions, such as fear of infection for themselves or their loved ones, difficulty in using the face mask, relational repercussions with patients or their families; (3) personal and working group strategies used to counteract the suffering attributable to COVID-19; (4) professionalism/nursing responsibilities in developing new rules and protocols, and (5) metaphors to describe their experiences. Conclusions The COVID-19 pandemic led to major changes in the nurses’ roles, but they showed resilience and generated a positive working climate. Implication for practice: Even in emergency situations, nursing administrations and policymakers must ensure that nurses receive adequate training and support to develop resilience and coping strategies.