The global expansion of highly pathogenic avian influenza A (H5N1), particularly the clade 2.3.4.4b lineage, has renewed urgent concerns about its pandemic potential in the context of its ongoing panzootic expansion and increasing cross-species transmission. Despite decades of preparedness initiatives, critical technological and structural gaps persist, especially in low- and middle-income countries (LMICs), where both vaccine access and sustainable manufacturing capacity remain limited. In this perspective, we examine key lessons from past influenza pandemics and global preparedness strategies, including the Global Action Plan for Influenza Vaccines, highlighting persistent challenges related to sustainable manufacturing capacity and equitable vaccine access. Additionally, we examine the potential of messenger RNA (mRNA) vaccine platforms to address these limitations, given their rapid design, scalable manufacturing, and adaptability to emerging pathogens. Moreover, we examine the role of neuraminidase (NA) as a complementary antigen capable of broadening immune protection and reducing viral transmission. Finally, we describe recent advances in Latin America, focusing on Argentina’s participation in the mRNA Technology Transfer Programme co-led by the World Health Organization (WHO) and the Medicines Patent Pool (MPP), as a model for strengthening regional manufacturing capacity and contributing to global pandemic preparedness. Together, these elements indicate that effective H5N1 pandemic preparedness will require the integration of improved antigen design, flexible mRNA platforms, and sustainable regional manufacturing systems aligned with global procurement strategies.