Abstract: Porcine reproductive and respiratory syndrome (PRRS) is one of the most viral diseases affecting the global pig industry, causing enormous annual economic losses. Although modified live virus (MLV) vaccines have been used for over three decades, the industry remains trapped in the dilemma of immunization that fails to prevent infection or block transmission. The core problem lies in the multi-dimensional immune evasion mechanisms evolved by porcine reproductive and respiratory syndrome virus (PRRSV), centered on the respiratory mucosa, while conventional vaccines suffer from three drawbacks: systemic immune bias, insufficient cross-protection, and safety risks. Moreover, the systematically evaluation systems over-rely on serological indicators, neglecting mucosal immunity—the first line of defense against viral invasion. This review systematically dissected the etiological characteristics of PRRSV and the molecular mechanisms underlying its mucosal immune evasion, evaluated the current status and limitations of conventional vaccines, and focused on breakthroughs in novel vaccine development and delivery technologies centered on mucosal immunity. It also reconstructed a three-dimensional integrated evaluation system incorporating "mucosal indicators + systemic immune quality + field transmission blockade". The core proposition of this review was to propose a new paradigm of active immune engineering: shifting from passively tracking viral variation to actively designing novel vaccine strategies based on "mucosa-targeted delivery + conserved antigen construction". By integrating technologies and innovating evaluation systems, a robust mucosal immune barrier can be established at the viral entry portal. This review provided a theoretical foundation and feasible reference for the effective control and even eradication of PRRS.