The alternative lengthening of telomeres (ALT) is a homology-directed repair (HDR)-based mechanism that maintains telomere length independently of telomerase by hijacking the canonical double-strand break (DSB) repair machinery. In ALT-positive cells, a RAD51-, MUS81-, and BLM-dependent recombination cascade copies telomeric tracts from sister chromatids, extrachromosomal telomeric circles (t-circles), or inter-chromosomal templates, thereby restoring a functional TTAGGG repeat array. This process is characterized by a distinct molecular signature:(1) chronic replication stress, manifested by elevated ATR-CHK1 signaling, R-loop accumulation, and fragile telomere phenotypes;(2) clustering of telomeric chromatin into ALT-associated PML bodies (APBs), which serve as SUMO-dependent recombination hubs enriched for SLX4-SLX1, MRE11-RAD50-NBS1, and FANCD2 complexes; and (3) global chromatin remodeling, marked by the eviction of histone H3.3 and its chaperones ATRX/DAXX, derepression of the long non-coding RNA TERRA, and acquisition of constitutive heterochromatin marks (H3K9me3/H4K20me3) along with the facultative heterochromatin mark H3K27me3. Together, these changes establish a chromatin environment permissive for homologous recombination. Importantly, these alterations are not merely passive by-products but are functionally required for homology search, strand invasion, and resolution of recombination intermediates. This is supported by CRISPR screens identifying ATRX, DAXX, and the SUMO E2 enzyme UBC9 as essential ALT fitness genes. While 85%-90% of human cancers re-express telomerase reverse transcriptase (TERT), the remaining 10%-15% are telomerase-null and rely exclusively on ALT for immortality. ALT tumors are enriched in osteosarcomas, glioblastomas, pancreatic neuroendocrine tumors, and aggressive soft-tissue sarcomas. In telomerase-negative somatic cells, progressive telomere shortening during each S phase eventually reaches a critical length, triggering a persistent DNA damage response (DDR) at chromosome ends. This activates the p53-p21 and p16INK4A-Rb tumor suppressor pathways, driving cells into stable replicative senescence. Although this telomere-length-dependent senescence acts as a potent barrier to malignant progression, recent single-cell analyses reveal that senescent fibroblasts and epithelial cells transiently display ALT-like features—such as accumulation of telomeric γH2AX/53BP1 foci, formation of APB-like PML condensates containing SUMOylated TRF1 and TRF2, and intermittent TERRA upregulation. These observations suggest that telomerase-negative tumors and senescent cells share a recombination-permissive chromatin state. Although senescent cells do not achieve net telomere elongation—likely due to intact p53/p16 checkpoints restraining unscheduled HDR—transient ALT activation may enable rare clonal escape. This further implies that ALT operates not only as a tumor-cell survival pathway but also as a protective mechanism against environmental stress. Indeed, spontaneous immortalization of TERT^-/- fibroblasts in vitro is preceded by stochastic ALT induction, indicating that stochastic recombination at dysfunctional telomeres can overcome senescence barriers and initiate malignant transformation. Consistent with this model, whole-genome sequencing of ALT-positive tumors frequently identifies early driver mutations in TP53, ATRX, and DAXX, which disable replicative-senescence checkpoints while simultaneously enhancing telomeric HDR. Here, we synthesize the convergent molecular features of ALT tumors and senescent cells, highlighting:(1) replication stress as a common initiating cue, (2) SUMO-dependent phase separation as a platform for telomere-templated recombination, and (3) epigenetic erosion of ATRX/DAXX-mediated heterochromatin as a rate-limiting step. Finally, we discuss therapeutic implications: (1) pharmacological inhibition of SUMO E1/E2 enzymes to prevent APB scaffold nucleation, (2) synthetic-lethal exploitation of replication stress via ATR/CHK1 inhibitors, and (3) immune-microenvironment-targeting strategies that remodel the senescence-associated secretory phenotype (SASP). Collectively, this review elucidates the mechanisms by which ALT regulates cellular senescence and tumorigenesis, offering druggable vulnerabilities and translational strategies for the clinical management of telomerase-negative tumors.