The deployment of nuclear power in Poland creates new opportunities to integrate reactors into multi-product energy systems that support decarbonization, energy security, and resource resilience. This study examines the potential of three nuclear reactor configurations for polygeneration applications in the Polish context: large pressurized water reactor (PWR) for electricity, district heating, and desalinated water; pressurized water reactor small modular reactor (PWR SMR) for electricity, heat, and cooling in coal-to-nuclear (C2N) transition scenario, and high-temperature gas-cooled reactor (HTGR ) for electricity, hydrogen production, and gasification. The analysis is framed by Poland’s energy strategy, which includes the planned deployment of large Generation III+ reactors, the need to decarbonize an extensive district heating sector, the ongoing dependence on coal-fired cogeneration, and the growing importance of low-carbon industrial energy carriers. Large coastal PWRs offer favorable conditions for coupling electricity generation with district heating and thermal seawater desalination through controlled heat extraction from the secondary loop. PWR SMRs provide a flexible option for replacing aging coal-based combined heat and power assets, particularly where existing infrastructure and local heat demand create opportunities for phased coal-to-nuclear transition. HTGRs, with their higher outlet temperatures, expand the scope of nuclear applications by enabling hydrogen production and the supply of high-temperature heat for gasification and other industrial processes. Synthesizing findings from the literature on nuclear multi-product systems, desalination, SMR deployment, coal-to-nuclear transition, hydrogen production, and nuclear-assisted industrial processes, this paper assesses the suitability of several distinct nuclear polygeneration configurations in Poland. The results indicate that large PWRs, PWR SMRs, and HTGRs offer complementary but separate application pathways for supporting electricity generation, district heating decarbonization, water supply, industrial heat, hydrogen production, and broader industrial transformation, depending on reactor type and end-use requirements.