Moral distress (MD) is frequently discussed in the nursing literature, but few studies include or focus on oncology nurses and those that do have inconsistent findings. Oncology care is distinct from other areas of practice in ways that are significant for the development of MD. This study, the first to focus on MD in Canadian oncology nurses, employed interpretive description to understand the experience of MD, the role of contextual factors, nurses’ responses to MD and perspectives on strategies to mitigate MD. Semi-structured interviews were conducted (via telephone or FaceTime) with 25 oncology nurses, recruited from the Canadian Association of Nurses in Oncology and via social media. Moral distress developed in a complex, non-linear multi-factorial fashion and was highly contextually situated. The experience and development of MD are described in the theme “’ You get used to a certain kind of horrible’… but the ‘wrong’ kind of horrible leads to moral distress.” Themes that describe the context of MD include “oncology nursing is hard,” “you can find your niche,” and “oncology nurses know.” “Humanness” was evident in the development of MD, responses to MD, suggested changes in practice, and is proposed as a generative mechanism for both the rewards and challenges of MD. Recommendations for attending to humanness in practice, considering new approaches to nursing and ethics education, and expanding organizational supports derive from the findings. Future research should consider the impact of interventions that support humanness in practice and examine the role of humanness in other settings and health care provider and administrator populations.