Abstract: Deep-sea hydrothermal vent polymetallic sulfide deposits exhibit significant enrichment in strategic metallic elements, including copper, zinc, gold, and silver, and critical rare-earth elements, such as cobalt, selenium, tellurium, and indium, which represents the most economically valuable mineral resources of the 21st century. These deposits, formed through complex hydrothermal processes involving mid-ocean ridge systems and back-arc spreading centers, demonstrate metal concentrations frequently exceeding conventional terrestrial ore deposits by several orders of magnitude, rendering them essential for future mineral resource security. Nevertheless, the harsh deep-sea environment characterized by water depths of 1500–5000 meters, extreme hydrostatic pressures up to 50 MPa, aggressive marine corrosion, and complex sulfide mineral assemblages presents formidable technical challenges throughout the complete “sampling—dissociation—extraction” processing chain for sustainable resource development. This study examines the current technological advances and identifies critical bottlenecks in this strategically significant research domain. Regarding sampling technologies, the evolution from conventional mechanical approaches to intelligent integrated systems is analyzed, encompassing multi-platform operations employing human-occupied vehicles (HOVs), remotely operated vehicles (ROVs), and autonomous underwater vehicles (AUVs). Critical sample preservation issues are identified as fundamental concerns, whereby recovered specimens experience severe temperature variations exceeding 300℃ and pressure differentials of 20–50 MPa during ascent from seafloor to surface, inevitably causing mineral phase transitions, oxidation reactions, and microstructural alterations that compromise analytical precision. The proposed innovations include the development of multiparameter monitoring systems with real-time sensing capabilities for temperature, pressure, pH, and electrochemical potential (Eh) coupled with adaptive sample preservation systems utilizing conservation protocols, including pressure compensation chambers, thermal regulation units, and inert gas protection systems, to maintain mineralogical stability and specimen integrity. Concerning dissolution mechanisms, the oxidative leaching kinetics of primary sulfide phases—including pyrite (FeS₂), chalcopyrite (CuFeS₂), and sphalerite (ZnS)—under coupled pressure-temperature conditions are investigated, encompassing elementary processes such as surface metal-sulfur bond dissociation, electrochemical electron transfer reactions, and aqueous ionic transport phenomena. The galvanic coupling effects characterized by electrochemical potential differences ranging from 0.1–0.5 V, synergistic dissolution enhancement, and competitive inhibition mechanisms within polymetallic sulfide assemblages are elucidated through electrochemical characterization methods. The necessity for establishing multiscale theoretical frameworks spanning five hierarchical levels from atomic-scale quantum mechanics to macroscopic continuum behavior, complemented by kinetic databases integrating density functional theory (DFT) calculations, molecular dynamics (MD) simulations, and in situ spectroscopic characterization techniques, is emphasized for a fundamental mechanistic understanding. Regarding environmentally sustainable extraction methodologies, the advantages and limitations of various green processing technologies are assessed, including biohydrometallurgical processes (specific energy consumption: 100–300 kW·h·t⁻¹), electrochemical extraction techniques (current density: 50–200 A·m⁻²), supercritical fluid extraction methods (operating parameters: 150–200 °C, 15–25 MPa), and microwave-assisted leaching technologies. The strategic implementation of integrated multi-technology synergistic processes is advocated, incorporating processing schemes such as combined biochemical leaching, microwave-ultrasonic coupling, and electrochemical-ultrasonic enhancement, targeting improvements in metal recovery efficiency of 10–20 percentage points and energy consumption reduction of 20%–30%. Four strategic research directions for future breakthroughs are proposed: (1) development of intelligent in situ sample preservation systems, (2) fundamental investigation of coupled pressure–temperature dissolution kinetics, (3) construction of integrated sustainable extraction processes achieving specific energy consumption < 1000 kW·h·t⁻¹ with metal recovery rates > 90%, and (4) establishment of digital twin control platforms with intelligent process optimization. These findings provide an essential theoretical foundation and practical technological guidance for deep-sea mineral resource development and represent critical contributions to national resource security and maritime technological advancement.