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Background This qualitative study aims to identify facilitators of and barriers to the implementation of Meaning-Centered Psychotherapy (MCP) by providers of mental health services to Latinos in the US and Latin America using the practical, robust implementation and sustainability model (PRISM). This information will be used to increase usability and acceptability of MCP for Latino patients with cancer and their providers in Latin America and the US. Methods A total of 14 Latino cancer patient mental health providers completed in-depth semi-structured interviews. Participants were recruited from 9 countries and 12 different sites. They provided feedback about barriers to and facilitators of implementation of MCP at the patient, provider, and clinic levels in their clinical setting. The qualitative data from the interviews was coded according to PRISM domains. Three analysts independently coded the transcripts; discrepancies between analysts were resolved through discussion and consensus. Results Based on PRISM, themes were: clinic environment (protected time for training and supervision), intervention characteristics (adapt the intervention using more simple language, include more visual aids, include more family-oriented content), patient (develop materials for the identification and screening of patients, provide educational materials, increase motivation and knowledge about psychotherapy, assess commitment to psychotherapy, adapt for the inpatient vs. outpatient setting), provider (receive interactive/participatory training, educational materials, ongoing supervision, have flexibility of delivering the intervention in a less structured manner, theoretical framework of the provider) and external environment (work at policy level to integrate services for oncology patients). Conclusion These qualitative data revealed potential facilitators and barriers of this intervention (MCP) on an international scale. Identified cultural, contextual, and healthcare systems factors illustrated the importance of examining pre-implementation needs prior to implementing a trial. We will design and plan a future RCT using the PRISM framework and these pre-implementation data. Plain Language Summary This study integrates frameworks of implementation science and cultural adaptation through the examination of pre-implementation contextual issues at the preparation phase of a cultural adaptation of a psychotherapeutic intervention, Meaning-Centered Psychotherapy (MCP), for Latinos with advanced cancer. By examining implementation needs early in the implementation process, during preparation, the intervention can be adapted in a way that attends to and addresses the providers’ most cited challenges in implementation: having a rigid protocol/structure, complexity of the intervention, disease burden preventing adherence to the intervention, transportation, and competing demands, and limited clinic space to offer the intervention.