Background: Tuberculosis (TB) poses a considerable challenge for people with HIV (PWH), especially in low- and middle-income countries. Even with the availability of effective preventive strategies such as tuberculosis preventive therapy (TPT), the implementation of these measures continues to fall short. Our study explores the perceptions of healthcare workers (HCWs) regarding the barriers and facilitators to TPT implementation in the Philippines and Indonesia. Methods: We performed 10 focus group discussions and four in-depth interviews with HCWs from June to December 2023. Each discussion and interview lasted between 45 and 120 min. Discussions explored HCWs’ perspectives on the policies, logistics, and prescribing practices related to TPT, as well as their personal experiences, concerns, and suggested improvements. Data were coded using MAXQDA24 qualitative software informed by the tenets of constructivist grounded theory. We organized themes using the Consolidated Framework for Implementation Research (CFIR), while contextualizing implementation determinants most pertinent to the local contexts. Results: Our findings revealed nuanced barriers and facilitators—marked by paradoxes—organized across three CFIR domains: the outer, inner, and individual domains of HIV-TB care. In the outer setting, barriers include limited patient knowledge and drug shortages, while facilitators involved national policies and external pressures from mass media and peer imitation. The inner setting was shaped by structural gaps—such as poor documentation, staff turnover, and procedural challenges in ruling out active TB—that affected patient trust, whereas open communication and role clarity supported TPT implementation. At the individual level, HCWs expressed high motivation but cited limited capacity due to lack of training and information to deliver effective TPT care. Conclusions: Our findings highlight implementation determinants to TPT implementation across outer, inner, and individual domains of HIV-TB care. Understanding how structural gaps, provider capacity, and patient trust intersect with supportive policies, and peer and mass media influences offer insights into the complex dynamics shaping TPT uptake and integration. Our study insights may inform policy adjustments and guide strategies to better integrate TPT into national health frameworks. © The Author(s) 2025.