We investigated nurses' experiences of hospital‐acquired pressure injury (PI) prevention in acute care services to better understand how PI prevention may be optimised. We used the Theoretical Domains Framework to systematically identify barriers and enablers to evidence‐based preventive practices as required by the International Guideline. This study was one element of a complex capacity building project on PI surveillance and prevention within the acute health service partners of Monash Partners Academic Health Science Centre, an accredited academic health partnership located in Melbourne, Australia. We adopted a qualitative descriptive design. We interviewed 32 nurses that provided care in intensive care units, general wards and COVID wards of four acute care services. Nurses were recruited from four large acute care services (three public, one private) located in Melbourne. Most of them worked with patients who were at high risk of hospital‐acquired PI on a daily basis. Interview transcripts were coded and analysed using thematic analysis guided by the Theoretical Domains Framework. The domains referred to most frequently by all participants included: Knowledge, Skills, Social/Professional Role and Identity, Beliefs about Capabilities, and Environmental Context and Resources. The key barriers discussed by nurses included gaps in nurses' knowledge and skills related to identification and staging of PI, heavy nursing workload and inadequate staffing levels, stigma and self‐blame related to PI identification, and exacerbating impacts of the COVID‐19 pandemic. Main facilitators discussed were training programmes, nursing audits and feedback, and teamwork. Participants suggested improvements including accessible and tailored training, visual reminders, and addressing heavy workloads and emotional barriers nurses face. Investing in tailored training initiatives to improve nurses' knowledge and organisational changes to address low level staffing and heavy workloads are urgently needed to support nurses in delivering optimal care and preventing hospital‐acquired PI.