Bacteria have myriad mechanisms to resist the infections of predatory mobile genetic elements such as bacteriophages 1, 2, 3. In turn, bacteriophages (or phages) have evolved a multitude of anti-defense strategies to uniquely circumvent these bacterial defenses 4, 5, 6, 7. Driven by the need for rapid replication in a hostile environment, most phages have a high coding capacity (i.e. minimal noncoding space) with essential genes that encode for phage replication and virion assembly, along with a small number of anti-defense mechanisms 8, 9, 10. ΦKZ-like jumbo phages (with genomes typically >200 kbp) emerge with a unique ability to thwart a plethora of intracellular DNA-targeting bacterial immune systems 11••, 12, which presumably contributes to their broad range of infectivity in diverse bacterial strains. Within the past decade, multidisciplinary investigations have revealed a complex developmental cycle of ΦKZ-like jumbo phages in bacteria. Most notably, ΦKZ-like jumbo phages encode two distinct intracellular macromolecular compartments that shield the phage genomic DNA from the bacterial cytoplasm whilst occluding immune nucleases. The membrane-bound ‘early phage infection (EPI) vesicle’ 13••, 14••, 15•• and the proteinaceous ‘phage nucleus’ 16••, 17 represent one of the most potent phage-encoded anti-immune mechanisms. In this review, we discuss these compartments — their architecture, their constituents, and their multifaceted roles in supporting jumbo phage replication and immune evasion. We also discuss additional anti-immune strategies encoded by these jumbo phages. Finally, we highlight the recent methodological advancements in the field that have propelled an extensive and rigorous dissection of a complicated phage infection cycle.