Cadmium (Cd) toxicity is a global concern that threatens soil health, agricultural productivity, and food safety. Diverse anthropogenic and natural sources contribute to Cd accumulation, significantly degrading the quality of agricultural soils. This toxicity disrupts plant physiological functions, primarily targeting the root system, and impeding plant growth and development. Selenium (Se), an essential micronutrient, has recently garnered significant attention for its potential to alleviate Cd-induced stress in plants. Selenium-mediated mitigation mechanisms involve competitive uptake, oxidative stress modulation, and soil microbial health enhancement, presenting a novel and sustainable strategy to combat Cd toxicity. This review aims to comprehensively analyze the interactions between selenium and cadmium within the soil–water–crop continuum. It explores the mechanistic insights into Se–Cd interactions, agronomic strategies for Se-mediated Cd toxicity mitigation, and soil and crop management practices that influence the dynamics of these elements. By synthesizing current knowledge, this chapter highlights the importance of integrating selenium applications into agricultural practices to improve crop resilience, enhance soil health, and ensure food safety.