Purpose: There is a paucity of information regarding health related quality of life (HRQoL) of young adults (YAs) with cancer and caregivers. Therefore, we characterize YA and caregiver perspectives on the impact of cancer and its treatment on HRQoL.; Methods: We conducted descriptive qualitative in-depth, semi-structured interviews with YAs receiving cancer care at an academic health center in Albuquerque, New Mexico (USA) and primary informal caregivers. The interviews, conducted from September through December 2015, focused on perspectives on the impact of the disease and its treatment in terms of physical and emotional effects, coping, and strategies to enhance HRQoL. We used an iterative thematic analysis approach to identify emergent themes and create a coding structure.; Results: We reached thematic saturation after interviewing 8 YAs and 8 caregivers. YAs and caregivers discussed cancer triggered challenges such as anxiety, depression, isolation, fear, and financial hardships. YAs and caregivers coped by maintaining positive perspectives, relying on friends and family, and prayer. Caregivers discussed how expectations for and experiences of a "good day" changed depending on their loved ones' stage of cancer treatment. YAs navigated challenges by focusing on activities and thoughts that provided meaning to their lives. YAs and caregivers suggested strategies to enhance HRQoL through patient/provider communication, support services, and decision making tools as potential mechanisms for grounding patient-centered interventions to improve cancer care.; Conclusions: Implications include the development and evaluation of informational and behavioral interventions tailored and targeted to address the pragmatic needs of YAs undergoing cancer treatment and informal caregivers.; Copyright © 2017 Elsevier Ltd. All rights reserved.