Background <p>Genetic improvement of rice for biotic stress is a major and continuous breeding objective owing to changing pest and disease scenarios. In response to climate change, an outbreak of new pathotypes and biotypes results in huge yield loss which directly impacts the economic stability and food security. The development of varieties with multiple resistance genes for a particular disease is the most effective approach to the combating mechanism against evolving pathogens and insects. Multiple resistance genes against blast (<i>Pi54</i>), bacterial leaf blight (<i>xa5</i>, <i>xa13</i>, <i>Xa21</i>), and brown plant hopper (<i>Bph17</i>, <i>Bph3</i>, <i>bph2</i>) were pyramided through marker-assisted forward breeding by attempting multiple crosses involving six parental lines. The F₄ lines were screened and the resistant lines were further reconfirmed at the F₅ stage through precise phenotyping and also by genotyping with trait-specific markers. Finally, the selected lines were evaluated for the agronomic performance.</p> Results <p>Four lines were selected from the population which carrying seven resistance genes against BL, BB, BPH with superior agronomic performance. Another line, x21302-239, harboring all the resistant genes and showing a resistant response in screening experiments for all three stresses, with marginal agronomic performance (single-plant yield: 33&#xa0;g), can be utilized as a desirable donor to develop elite rice cultivars with multiple biotic stress resistance.</p> Conclusions <p>Homozygous genetic background is more favorable for epidemic outbreak in a short period of time in comparison with the population of multiple genetic background. Since this complex genetic background disturbs the infectious cycle of the pathogen. So that a variety or a hybrid which developed from multiple parental lines are notable for their durable resistance than the monogenic resistance variety.</p>