Anaerobic ammonium oxidation (anammox) process is a highly effective and economic technology for nitrogen removal from wastewater. However, the slow growth of anammox bacteria and sludge flotation often hinder its field application. Ion adsorption and crystal precipitation can potentially promote the sludge granulation and hence address the above issues. This study investigated two approaches to support anammox granulation through Mg2+ adsorption and magnesium ammonium phosphate (MAP) precipitation. Mg2+ addition improved the specific anammox activity (SAA) by 4.09 to 4.75-fold compared to MAP-mediated ones, which could be explained by the upregulations of nitrogen and inorganic carbon metabolisms. The active extracellular polymeric substances generation at metabolites level may also favor the granulation in Mg2+-mediated anammox. However, sludge loss halted the continuous size increase of sludge. Differently, MAP promoted granulation by physically increasing the granular density, which allowed for a greater retention of sludge within the reactor. However, the co-growth of MAP precipitates with anammox may lead to mass transfer limitations, resulting in down-regulated gene expressions and metabolites in inorganic carbon metabolism, which negatively impacted the SAA. Overall, both strategies achieved comparable nitrogen removal capacities. Nevertheless, the co-growth of MAP and anammox was promising for effectively mitigating sludge flotation. Our study provided strategies and omics-based evidences for anammox granulation and activity variations, benefiting anammox practical applications.