Background: Cancer is a major global public health challenge, imposing severe health and economic burdens on healthcare systems and households. East Khasi Hills District in North-East India exhibits a unique cancer profile with elevated incidence rates of upper aerodigestive and gastrointestinal malignancies.  Objective: This study examines the epidemiological prevalence, age-wise distribution, and multidimensional socio-economic impacts of cancer in East Khasi Hills District, Meghalaya State.  Methods: Secondary epidemiological registry data covering major cancer types (N = 2,228 males; N = 1,240 females) were obtained from the Population-Based Cancer Registry (PBCR), East Khasi Hills, and standardized using Z-score analysis to identify age-specific vulnerability patterns. Primary survey data were collected from 50 cancer patients selected via stratified random sampling using structured questionnaires and personal interviews. Multivariate factor analysis was executed via Principal Component Analysis (PCA) with Varimax rotation on 35 socio-economic, clinical, and healthcare accessibility variables using IBM SPSS.  Result: Oesophageal cancer is the predominant malignancy among both male (43%, 973 cases) and female (32%, 467 cases) patients. Peak cancer vulnerability is concentrated in middle and older adulthood, specifically the 45–54 age group for males (Z = 1.80 for oesophageal cancer at 45–49 years) and 45–64 age group for females (Z = 1.66 at 55–59 years). PCA extracted 11 principal dimensions with eigenvalues > 1.0, explaining 78.52% of total cumulative variance.  Conclusion: The high concentration of cancer cases among middle-aged adults combined with catastrophic out-of-pocket costs underscores the critical need for targeted age-specific screening programs (ages 40–64) and institutional financial assistance mechanisms to protect vulnerable households from medical impoverishment.